胰岛素对糖尿病小鼠小肠功能的影响

Objective To investigate the effects of regular insulin (RI)on duodenal smooth muscle in diabetic mice. Methods Diabetes mellitus (DM) model was established by intraperitoneal injection of 150 mg/kg streptozotocin (STZ) in male BALB/c mice. The model mice were divided into DM group and DM treated with RI group with 6 each. Meanwhile, 6 normal mice were served as controls. The mice in treatment group were intraperitoneally injected with 40 U/kg of RI daily.Whereas the mice in DM and control groups were intraperitoneally injected with phosphate buffer solution (pH = 7. 40). After 6 weeks, the small intestinal transit rate of mice was determined by lavage of Indian ink. Interstitial cells of cajal (ICC) in duodenal myenteric plexus were counted using immunohistochemical staining. Slow waves of duodenal smooth muscle cells were recorded with intracellular recordings. Data were analysed by SPSS 17.0 software, and comparisons among three groups were done using LSD test. Results After intervention for 6 months, the clinical presentations,such as more water and food intake and polyuria, were improved in treatment group. The body weight was increased in treatment group [(23.33±3.13) g] compared with DM group [(15.42±1.40) g,P＜0.01] ,but dereased compared with control group [(26.78 ± 2.09) g, P＜0.05]. The level of blood glucose in DM group was significantly higher than that in control and treatment groups(P＜0.01). Small intestine transmission rate was significantly reduced in DM group than that in control and treatment groups (P＜0.01), but it was slower in treatment group than that in control group (P＜ 0. 01 ). Immunohistochemical study showed that the number of c-kit positive cells reduced obviously in DM group than that in control group and treatment group (P＜0.05), whereas it was lower in treatment group than that in control group (P ＜ 0.05). The slow wave frequency and amplitude of duodenal smooth muscle cells in DM group were reduced when compared with control and treatment groups (P＜0.01) and both were lower in treatment group than that in control group (P＜0. 01 ). Conclusion The findings indicate that DM mice have gastrointestinal dysmotility and exogenous insulin may improve small intestinal dysmotility in DM mice.     

神经调节辅助通气对急性呼吸窘迫综合征兔呼吸机相关性膈肌功能障碍的影响

目的 探讨神经调节辅助通气(NAVA)对ARDS呼吸机相关性膈肌功能障碍(VIDD)的预防作用.方法 将20只成年新西兰大白兔按随机数字表法分为对照组、容量控制通气组(VC组)、压力支持通气组(PSV组)和NAVA通气组(NAVA组),每组5只.VC、PSV及NAVA组在机械通气4 h后取膈肌标本,对照组麻醉后立即取膈肌标本.测定各组膈肌中丙二醛、超氧化物歧化酶(SOD)以及还原型谷胱甘肽(GSH)含量,观察各组膈肌纤维病理结构的改变.结果 (1)丙二醛:NAVA组膈肌中丙二醛含量为(0.28±0.19)nmol/mg,与对照组的(0.15±0.06)nmol/mg、PSV组的(0.30±0.11)nmol/mg比较,差异无统计学意义(F=2.730,P＞0.05);VC组膈肌中丙二醛含量为(0.40±0.16)nmol/mg,明显高于对照组(P＜0.05).(2)SOD:NAVA组膈肌中SOD含量为(94±9)U/mg,与对照组的(111±12)U/mg、PSV组的(93±4)U/mg比较,差异无统计学意义(F=4.422,P＞0.05);VC组膈肌中SOD含量为(80±21)U/mg,明显低于对照组(P＜0.05).(3)GSH:NAVA组膈肌中丙二醛含量为(5.6±1.0)mg/g,与对照组的(5.3±1.0)mg/g、PSV组的(4.5±1.2)mg/g比较,差异无统计学意义(F=3.001,P＞0.05);VC组膈肌中GSH含量为(3.3±1.7)mg/g,明显低于对照组(P＜0.05).(4)光镜观察:VC组出现肌纤维变性、坏死,部分肌纤维萎缩;NAVA、PSV组以及对照组肌纤维形态基本正常.(5)电镜观察:VC组肌原纤维断裂,线粒体肿胀;NAVA组、PSV组以及对照组超微结构无明显异常.(6)膈肌纤维横截面积:NAVA组平均肌纤维横截面积(像素)为2573±278,与对照组的3070+175、PSV组的2508±670比较,差异无统计学意义(F=1.775,P＞0.05);VC组Ⅱ型肌纤维横截面积为2210±971,明显低于对照组的3477±187(P＜0.05).结论 与控制通气相比较,NAVA可减轻ARDS膈肌氧化应激、膈肌萎缩和膈肌结构损伤,NAVA较控制通气更能预防VIDD.

Abstract：

Objective To evaluate the effect of neurally adjusted ventilatory assist (NAVA) on prevention of ventilator-induced diaphragmatic dysfunction (VIDD) in ARDS rabbits.Methods Twenty New Zealand white rabbits were randomly divided into 4 groups: ( 1 ) control group ( n = 5 ); ( 2 ) Volume control (VC) group ( n = 5 ); ( 3 ) Pressure support ( PSV ) group ( n = 5 ); (4) NAVA group ( n = 5 ).In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation.Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing.In all rabbits, malondialdehyde ( MDA), superoxide disrmutase (SOD) and glutathione(GSH) of diaphragm were measured.Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area (CSA) of diaphragm fiber.Results (1)MDA: Compared with the control [(0.15 ±0.06)nmol/mg], PSV group[(0.30 ±0.11)nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [( 0.28 ± 0.19 )nmol/mg] (F = 2.730, P ＞ 0.05).MDA in VC group [(0.40 ±0.16)nmol/mg] was significantly higher than the control group (P＜0.05).(2) SOD: Compared with control [( 111 ± 12) U/mg], PSV group [(93 ± 4) U/mg], there was no significant difference in SOD of diaphragm in NAVA group [( 94 ± 9 )U/mg] (F=4.422,P ＞0.05).SOD in VC group [(80 ±21 )U/mg] was significantly lower than the control group(P ＜0.05).(3)GSH: Compared with control [(5.3 ± 1.0)mg/g] and PSV group [(4.5 ±1.2)mg/g], there was no significant difference in GSH of diaphragm in NAVA group [(5.6 ± 1.0) mg/g](F =3.001 ,P ＞ 0.05 ).GSH in VC group [(3.3 ± 1.7)mg/g] is significantly lower than control and NAVA groups ( P ＜ 0.05 ).( 4 ) Light microscope: In VC group, many changes were observed in the muscle, such as myofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups.(5)Electron microscope: In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria.(6)CSA of diaphragm fiber: Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group ( P ＞ 0.05 ); The CSA of type Ⅱ fibers in VC group was markedly lower than control group ( P ＜ 0.05 ) .Conclusions Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.     

胰岛素对糖尿病小鼠小肠功能的影响

Objective To investigate the effects of regular insulin (RI)on duodenal smooth muscle in diabetic mice. Methods Diabetes mellitus (DM) model was established by intraperitoneal injection of 150 mg/kg streptozotocin (STZ) in male BALB/c mice. The model mice were divided into DM group and DM treated with RI group with 6 each. Meanwhile, 6 normal mice were served as controls. The mice in treatment group were intraperitoneally injected with 40 U/kg of RI daily.Whereas the mice in DM and control groups were intraperitoneally injected with phosphate buffer solution (pH = 7. 40). After 6 weeks, the small intestinal transit rate of mice was determined by lavage of Indian ink. Interstitial cells of cajal (ICC) in duodenal myenteric plexus were counted using immunohistochemical staining. Slow waves of duodenal smooth muscle cells were recorded with intracellular recordings. Data were analysed by SPSS 17.0 software, and comparisons among three groups were done using LSD test. Results After intervention for 6 months, the clinical presentations,such as more water and food intake and polyuria, were improved in treatment group. The body weight was increased in treatment group [(23.33±3.13) g] compared with DM group [(15.42±1.40) g,P＜0.01] ,but dereased compared with control group [(26.78 ± 2.09) g, P＜0.05]. The level of blood glucose in DM group was significantly higher than that in control and treatment groups(P＜0.01). Small intestine transmission rate was significantly reduced in DM group than that in control and treatment groups (P＜0.01), but it was slower in treatment group than that in control group (P＜ 0. 01 ). Immunohistochemical study showed that the number of c-kit positive cells reduced obviously in DM group than that in control group and treatment group (P＜0.05), whereas it was lower in treatment group than that in control group (P ＜ 0.05). The slow wave frequency and amplitude of duodenal smooth muscle cells in DM group were reduced when compared with control and treatment groups (P＜0.01) and both were lower in treatment group than that in control group (P＜0. 01 ). Conclusion The findings indicate that DM mice have gastrointestinal dysmotility and exogenous insulin may improve small intestinal dysmotility in DM mice.     

抗炎与抗氧化联合治疗在卒中急性期的应用

目的 探讨联合抗炎、抗氧化治疗在卒中急性期的作用.方法 将128例急性缺血性卒中患者随机分为对照组(71例)与联合治疗组(57例),检测治疗前后血浆标志物水平,评价治疗前后神经功能及生活能力,进行组间及组内比较,观察联合治疗对急性期血浆标志物及早期临床预后的影响.结果 治疗前联合治疗组基质金属蛋白酶(MMP)-9水平[(3.23±0.99)ng/L]高于对照组[(2.82±1.21)ng/L,P＜0.05];联合治疗组氧化低密度脂蛋白(ox-LDL)抗体水平治疗前[(0.08±0.01)U/m1]高于治疗后[(0.07±0.01)U/ml,P＜0.05];对照组治疗前美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分[(5.76±6.61)分比高于治疗后(4.22±5.45)分,P＜0.05].结论 联合治疗可以降低缺血性卒中急性期患者血浆MMP-9及ox-LDL抗体水平,但未明显改善早期预后.

Abstract：

Objective Research the effect of anti-inflammatory and anti-oxidation drugs on acute stroke patients. Methods 128 patients with acute ischemic stroke are divided into two groups- combined treatment group (71) and control (57). Test serum biomarkers and evaluate neurological function and living ability before and after therapy, compare between groups and intra-group. To observe the effects of combined therapy on serum biomarkers and prognosis in acute stage. Results ( 1 ) MMP-9 of combined treatment group (3.23 ±0. 99) ng/L is higher than control (2. 82 ± 4. 21 )ng/L before therapy (P ＜0. 05). (2) The level of pre-treatment ox-LDL-Ab in combined treatment group ( 0. 08 ± 0. 01 ) U/ml higher than posttreatment (0. 07 ±0. 01 ) U/ml (P ＜ 0. 05 ). The level of pre-treatment NIHSS in control group (5.76 ±6.61) score higher than post-treatment (4.22 ±5.45) score,P＜0.05. Conclusion Combined treatment can degrade serum MMP-9 and ox-LDL in acute ischemic stroke patients, but it can't obviously improve the earlier prognosis.     

Shugan-decoction relieves visceral hyperalgesia and reduces TRPV1 and SP colon expression

AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P&g     

胰岛素对糖尿病小鼠小肠功能的影响

目的 探讨胰岛素(regular insulin,RI)对糖尿病(DM)小鼠小肠功能的影响.方法 一次性给予雄性BALB/c小鼠链脲佐菌素(STZ,150 mg/kg)腹腔注射造模.将造模成功小鼠分为DM组6只,DM+RI组6只,另选血糖正常小鼠6只为对照组.DM+RI组给予RI 40U·kg-1·d-1皮下注射,对照组和DM组每天给予等量的磷酸盐缓冲液(pH=7.4)腹腔注射.所有小鼠干预6周结束后,给予印度墨水灌胃测定胃肠传输速率.免疫组织化学法检测各组小鼠十二指肠组织的c-kit阳性细胞数目.最后处死所有小鼠,用细胞内记录技术记录各组小鼠十二指肠平滑肌细胞内慢波的变化.采用SPSS 17.0软件分析,多组资料间比较采用LSD检验.结果 干预6周后,DM+RI组的多饮、多食、多尿症状比DM组减轻,体重较DM组明显增加[(23.33±3.13)g比(15.42±1.40)g,P＜0.01],但比对照组降低[(26.78±2.09)g,P＜0.05].第6周DM组血糖值显著高于对照组(P＜0.01),但比DM+RI组显著升高(P＜0.01).DM组小肠推进率比DM+RI组和对照组明显降低(P值均＜0.01);DM+RI组也较对照组降低(P＜0.01).光镜下观察到DM组c-kit阳性细胞数明显低于DM+RI组和对照组(P值均＜0.05),DM+RI组比正常组减少(P＜0.05).DM组慢波频率比DM+RI组和对照组显著降低(P值均＜0.01),而DM+RI组慢波频率比对照组降低(P＜0.01).DM组慢波波幅比DM+RI组和对照组明显降低(P值均＜0.01),而DM+RI组慢波波幅比对照组降低(P＜0.01).结论 DM小鼠存在胃肠动力障碍,外源性RI可能对DM小鼠小肠动力障碍有一定的改善作用.

Abstract：

Objective To investigate the effects of regular insulin (RI)on duodenal smooth muscle in diabetic mice. Methods Diabetes mellitus (DM) model was established by intraperitoneal injection of 150 mg/kg streptozotocin (STZ) in male BALB/c mice. The model mice were divided into DM group and DM treated with RI group with 6 each. Meanwhile, 6 normal mice were served as controls. The mice in treatment group were intraperitoneally injected with 40 U/kg of RI daily.Whereas the mice in DM and control groups were intraperitoneally injected with phosphate buffer solution (pH = 7. 40). After 6 weeks, the small intestinal transit rate of mice was determined by lavage of Indian ink. Interstitial cells of cajal (ICC) in duodenal myenteric plexus were counted using immunohistochemical staining. Slow waves of duodenal smooth muscle cells were recorded with intracellular recordings. Data were analysed by SPSS 17.0 software, and comparisons among three groups were done using LSD test. Results After intervention for 6 months, the clinical presentations,such as more water and food intake and polyuria, were improved in treatment group. The body weight was increased in treatment group [(23.33±3.13) g] compared with DM group [(15.42±1.40) g,P＜0.01] ,but dereased compared with control group [(26.78 ± 2.09) g, P＜0.05]. The level of blood glucose in DM group was significantly higher than that in control and treatment groups(P＜0.01). Small intestine transmission rate was significantly reduced in DM group than that in control and treatment groups (P＜0.01), but it was slower in treatment group than that in control group (P＜ 0. 01 ). Immunohistochemical study showed that the number of c-kit positive cells reduced obviously in DM group than that in control group and treatment group (P＜0.05), whereas it was lower in treatment group than that in control group (P ＜ 0.05). The slow wave frequency and amplitude of duodenal smooth muscle cells in DM group were reduced when compared with control and treatment groups (P＜0.01) and both were lower in treatment group than that in control group (P＜0. 01 ). Conclusion The findings indicate that DM mice have gastrointestinal dysmotility and exogenous insulin may improve small intestinal dysmotility in DM mice.     

Establishment of model of visceral pain due to colorectal distension and its behavioral assessment in rats

AIM: To establish a visceral pain model via colorectal distension (CRD) and to evaluate the efficiency of behavioral responses of CRD by measuring the score of abdominal withdrawal reflex (AWR) in rats. METHODS: Thirty-eight male SD rats weighing 180-240g were used to establish the visceral pain model. The rat was inserted intra-anally with a 7 cm long flexible latex balloon under ether anesthesia, and colorectal distensions by inflating the balloon with air were made 30 min after recovering from the anesthesia. Five AWR scores (AWRO to AWR4) were used to assess the intensity of noxious visceral stimuli. It was regarded as the threshold of the minimal pressure (kPa). For abdominal flatting was induced by colorectal distension. RESULTS: A vigorous AWR to distension of the descending colon and rectum was found in 100% of the awake rats tested. The higher the pressure of distension, the higher the score of AWR. The distension pressures of 0, 2.00, 3.33, 5.33 and 8.00 kPa produced different AWR scores (P<0.05). The pain threshold of AWR was constant for up to 80 min after the initial windup (first 1-3 distensions), the mean threshold was 3.69±0.35 kPa. Systemic administration of morphine sulfate elevated the threshold of visceral pain in a dosedependent and naloxone reversible manner. CONCLUSION: Scoring the AWR during colorectal distensions can assess the intensity of noxious visceral stimulus. Flatting of abdomen (AWR 3) to CRD as the visceral pain threshold is clear, constant and reliable. This pain model and its behavioral assessment are good for research on visceral pain and analgesics.     

慢性阻塞性肺疾病大鼠肺树突细胞数量及成熟度变化与慢性炎症的关系

目的 观察香烟烟雾暴露对大鼠肺组织树突细胞数量、成熟度及肺组织慢性炎症变化的影响.方法 将30只雄性F344大鼠按随机数字表法分为香烟烟雾暴露组(暴露组)、断烟组和健康对照组(对照组),每组10只.采用香烟烟雾暴露法建立大鼠COPD模型,HE染色法检测大鼠气道炎症病理评分及肺泡平均内衬间隔,免疫组织化学ABC法观察大鼠肺组织中CD11c+、CD86+和CD8+ T细胞的分布及数量变化,流式细胞术检测CD11c+/CD86+和CD11c+/主要组织相容性复合体(MHC)Ⅱ+与CD11c+树突细胞比值.结果 暴露组和断烟组大鼠肺组织中出现COPD特征性病理改变,气道炎症病理评分[(390±33)分和(324±28)分]及肺泡平均内衬间隔[(68±11)μm和(58±9)μm]明显高于对照组[(56±13)分和(36±6)μm],差异均有统计学意义(F值分别为459.85和34.03,均P＜0.05).暴露组和断烟组大鼠CD11c+树突细胞阳性率[(1.47±0.12)%和(1.30±0.17)%]及CD86+树突细胞阳性率[(1.26±0.18)%和(1.02±0.08)%]均明显高于对照组[(0.96±0.08)%和(0.65±0.03)%],差异均有统计学意义(F值分别为6.55和30.26,均P＜0.05);暴露组和断烟组大鼠CD8+T细胞阳性率[(2.72±0.15)%和(2.35±0.23)%]均明显高于对照组[(1.39±0.11)%],差异有统计学意义(F=16.07,P＜0.05);暴露组和断烟组大鼠CD11c+/CD86+树突细胞及CD11c+/MHCⅡ+树突细胞占CD11c+树突细胞比例[(5.5±0.4)%和(4.8±0.4)%]及[(4.2±0.3)%和(3.3±0.3)%]明显低于对照组[(8.0±0.5)%和(6.1±0.5)%],差异均有统计学意义(F值分别为14.34和12.82,均P＜0.05).暴露组与断烟组上述各项指标比较,差异均无统计学意义(t值为1.10～2.11,均P＞0.05).结论 香烟烟雾暴露诱导COPD大鼠肺组织中树突细胞数量明显增加,成熟度明显下降,断烟后此趋势无明显变化,且以CD8+ T细胞浸润为主的慢性炎症反应持续存在,提示树突细胞数量变化及成熟异常可能参与了COPD慢性炎症迁延进展.

Abstract：

Objective To evaluate the changes in the number and maturation of lung tissue dendritic cells (DCs) and to assess the chronic inflammation in a cigarette smoke-induced COPD model in rats.Methods Thirty male F344 rats were randomly divided into 3 groups (n = 10):a control group, a smoke-exposure group and a smoking cessation group.Rat lung pathomorphological changes were observed by hematoxylin-eosin (HE) stain.Lung tissue CD11c+ DCs, CD85+ DCs and CD8+ T cell numbers were observed by immunohistochemisty method.Flow cytometry was used for detection of CD11c+/CD86+ DCs and CD11c+/MHCⅡ + DCs proportions.Results The airway inflammatory pathological score and the mean linear intercept (MLI) obtained from he smoke-exposure group and the smoking cessation group (390 ± 33,324 + 28 ) and[(68 ± 11 ) μm, (58 ± 9) μm]were higher than those in the control group ( 56 ± 13 ) and ( 36 ± 6 ) μm( F =459.85 and 34.03, all P ＜0.05 ).In the smoke-exposure group and the smoking cessation group, the positive rate of CD11c+ DCs[(1.47 ±0.12)%, (1.30 ±0.17)%], and the positive rate of CD86+ DCs [( 1.26 ± 0.18 ) %, ( 1.02 ± 0.08 ) %]were higher than those in the control group[( 0.96 ± 0.08 ) %,(0.65 ± 0.03 ) %]( F = 6.55 and 30.26, all P ＜ 0.05 ), but there was no significant difference between the smoke-exposure group and the smoking cessation group ( t = 1.10 and 1.47, all P ＞ 0.05 ).In the smoke-exposure group and the smoking cessation group, CD8+ T positive rate[(2.72 ±0.15)%, (2.35 ±0.23)%]was higher than that in the control group[(1.39 ±0.11)%](F = 16.07, P ＜0.05).CD11c+/CD86+ DCs and CD11c+/MHC Ⅱ+DCs percentages[(5.5 ±0.4)%, (4.8 ±0.4)%],[(4.2 ±0.4)%, (3.3±0.3 )%]decreased in the smoke-exposure group and the smoking cessation group as compared to the control group[(8.0±0.5 ) %, (6.1 ± 0.5 ) %]( F = 14.34 and 12.82, all P ＜ 0.05 ).There was no significant difference between all the above index from the smoke-exposure group and the smoking cessation group ( t = 1.10 and 2.11, all P ＞ 0.05 ).Conclusions Cigarette smoke exposure induced increased DCs transmigrated and influenced the maturation of DCs in COPD rats.Even after smoking cessation, non-specific chronic inflammation was still present, suggesting that DCs number and maturation abnormality may be involved in the chronic inflammation of COPD.     

姜黄素对大鼠肠纤维化的作用及其机制研究

目的 探讨姜黄素在三硝基苯磺酸(TNBS)诱导的大鼠结肠纤维化中的抗纤维化作用和机制.方法 SD大鼠40只随机分组,模型组(10只)、治疗组(10只)和对照组(10只)分别于第1、8、15、22和29天予TNBS 10 mg、15 mg、20 mg、25 mg和30 mg灌肠,另取10只大鼠给予50%乙醇灌肠,作为阴性对照(正常组).从实验周期第1天起,治疗组大鼠每日予姜黄素30 mg/kg腹腔注射,对照组每日予0.9%NaCl腹腔注射,模型组和正常组不予处理.采用HE染色及Masson胶原三色染色观察大鼠结肠组织损伤和纤维化变化,采用ELISA法检测结肠黏膜中Th1/Th2型细胞因子IL-2、TNF-α、IL-4、IL-17的含量,采用荧光定量PCR法检测结肠黏膜中肠纤维化相关细胞因子如转化生长因子(TGF)-β1、结缔组织生长因子(CTGF)、Smad3、胶原Ⅰ、ⅢmRNA的表达.结果 模型组与对照组大鼠结肠组织大体损伤评分[(6.14±1.07)分,(6.17±1.47)分]及组织损伤评分[(8.42±1.40)分,(8.17±1.47)分]、胶原面积比(36.59%±4.07%,37.18%±4.05%)较正常组[分别为(2.13±0.64)分,(2.25±1.28)分和25.43%±5.39%]明显升高(均P＜0.05).模型组与对照组大鼠黏膜组织中IL-2[(378.25±29.90)ng/L,(410.06±64.74)ng/L]、TNF-α[(87.11±23.85)ng/L,(100.41±12.59)ng/L)]、IL-17[(47.80±5.62)ng/L,(41.45±2.12)ng/L]含量及TGF-β1(4.71%±2.71%,4.12%±3.01%)、CTGF(10.33%±6.99%,11.46%±4.72%)、Smad3(9.35%±7.32%,10.11%±3.80%)、胶原Ⅰ(1.52%±1.11%,1.57%±1.35%)、胶原Ⅲ(3.04%±1.33%,3.03%±3.53%)mRNA表达量较正常组[分别为(179.74±20.73)ng/L,(35.47±7.13)ng/L,(14.48±7.52)ng/L和0.90%±1.13%,0.53%±0.47%,0.62%±0.44%,0.16%±0.09%,0.18%±0.10%]均明显升高(均P＜0.05).而治疗组大鼠结肠组织大体损伤评分[(4.00±1.07)分]及组织损伤评分[(5.13±1.46)分]、胶原面积比(30.01%±7.56%),IL-2[(223.91±28.04)ng/L]、TNF-α[(44.19±4.77)ng/L]、IL-17[(14.89±4.31)ng/L]含量和TGF-β1(0.85%±0.76%)、CTGF(1.56%±1.13%)、Smad3(3.62%±3.03%)、胶原Ⅰ(0.40%±0.31%)、胶原Ⅲ(0.60%±1.02%)mRNA表达量较模型组及对照组明显降低(P＜0.05),与正常组无明显差异(P＞0.05).结论 姜黄素可通过降低细胞因子的过度表达,减轻大鼠结肠炎症,从而抑制过度"损伤-修复"所致的组织纤维化.

Abstract：

Objective To investigate the anti-fibrotic effects of curcumin in trinitrobenzene sulphonic acid (TNBS) induced intestinal fibrosis in rats and its mechanism. Methods Forty SD rats were randomly divided into model group, treatment group, control group and normal group with 10each. Except the normal group, the other three groups were given 10, 15, 20, 25 and 30 mg of TNBS enema on the 1st, 8 th, 15th, 22nd and 29th days,respectively. The rats in treatment group were intraperitonealy injected with 30 mg/kg of curcumin daily. Control group was injected with 0. 9%NaCl solution and normal group received an equal volume of 50% ethanol enema without any treatment. The damage and fibrosis of colon were detected with HE staining and Masson collagen staining, respectively. The contents of interleukin (IL) -2, tumor necrosis factor (TNF) -α, IL-4 and IL-17 in colon were measured by enzyme-link immunosorbent analysis (ELISA). The expressions of intestinal fibrosis related cytokines such as transforming growth factor (TGF) -β1, connective tissue growth factor (CTGF), Smad3, collagen Ⅰ and collagen Ⅲ mRNA were determined by FQ-PCR.Results The macroscopic and micrpscopic colonic damage scores and collagen area were significantly higher in model group (6.14 ± 1.07, 8. 42 ± 1.40 and 36. 59% ± 4.07%, respectively) and control group (6.17 ± 1.47, 8. 17 ±1.47 and 37.18 %±4.05 %, respectively) than those in normal group (2.13±0.64, 2.25±1.28 and 25.43%±5.39% ,respectively)(P＜0.05). Contents of IL2, TNF-α, IL-17, as well as expressions of intestinal fibrosis related cytokines including TGF-β1, CTGF,Smad3, collagen Ⅰ and Ⅲ mRNA were also higher in model group [(378. 25±29. 90) ng/L,(87.11±23.85) ng/L, (47.80±5.62) ng/L, 4.71%±2.71%,10.33%±6.99%,9.35%±7.32%,1.52% ± 1.11% and 3.04% ±1.33%, respectively] and control group [(410. 06 ± 64.74) ng/L,(100.41±12.59) ng/L, (41.45±2. 12) ng/L, 4. 12%±3.01%,11.46%±4.72%,10. 11%±3.80%,1. 57% ± 1. 35% and 3. 03% ± 3. 53%, respectively] in comparision with normal group [(179.74±20. 73) ng/L, (35. 47±7. 13) ng/L, (14. 48±7. 52) ng/L and 0. 90%± 1. 13%,0.53%±0.47%, 0. 62%±0. 44%, 0. 16%±0. 09% and 0. 18%±0. 10%, respectively] (P＜0.05). While in treatment group, the macroscopic (4.00 ± 1.07 ) and micrpscopic (5. 13 ± 1.46)colonic damage scores, collagen area (30.01%±7.56%), contents of IL-2 [(223.91±28.04) ng/L],TNF-α [(44.19±4. 77) ng/L] and IL-17 [(14.89±4. 31) ng/L], expressions of TGF-β1 (0.85%±0.76%), CTGF (1.56%±1.13%), Smad3 (3.62%±3.03%), collagen Ⅰ (0.40%±0.31%) and Ⅲ (0.60 % ± 1.02 % ) mRNA were much lower than those in model group and control group (P＜0.05 ), but similar to those in normal group (P＞ 0.05 ). Conclusions Curcumin can inhibit intestinal fibrosis caused by excessive "wound-healing" reaction via reducing the overexpression of cytokines in colonic mucosa and attenuating the inflammation of colon.     

神经调节辅助通气对急性呼吸窘迫综合征兔呼吸机相关性膈肌功能障碍的影响

Objective To evaluate the effect of neurally adjusted ventilatory assist (NAVA) on prevention of ventilator-induced diaphragmatic dysfunction (VIDD) in ARDS rabbits.Methods Twenty New Zealand white rabbits were randomly divided into 4 groups: ( 1 ) control group ( n = 5 ); ( 2 ) Volume control (VC) group ( n = 5 ); ( 3 ) Pressure support ( PSV ) group ( n = 5 ); (4) NAVA group ( n = 5 ).In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation.Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing.In all rabbits, malondialdehyde ( MDA), superoxide disrmutase (SOD) and glutathione(GSH) of diaphragm were measured.Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area (CSA) of diaphragm fiber.Results (1)MDA: Compared with the control [(0.15 ±0.06)nmol/mg], PSV group[(0.30 ±0.11)nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [( 0.28 ± 0.19 )nmol/mg] (F = 2.730, P ＞ 0.05).MDA in VC group [(0.40 ±0.16)nmol/mg] was significantly higher than the control group (P＜0.05).(2) SOD: Compared with control [( 111 ± 12) U/mg], PSV group [(93 ± 4) U/mg], there was no significant difference in SOD of diaphragm in NAVA group [( 94 ± 9 )U/mg] (F=4.422,P ＞0.05).SOD in VC group [(80 ±21 )U/mg] was significantly lower than the control group(P ＜0.05).(3)GSH: Compared with control [(5.3 ± 1.0)mg/g] and PSV group [(4.5 ±1.2)mg/g], there was no significant difference in GSH of diaphragm in NAVA group [(5.6 ± 1.0) mg/g](F =3.001 ,P ＞ 0.05 ).GSH in VC group [(3.3 ± 1.7)mg/g] is significantly lower than control and NAVA groups ( P ＜ 0.05 ).( 4 ) Light microscope: In VC group, many changes were observed in the muscle, such as myofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups.(5)Electron microscope: In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria.(6)CSA of diaphragm fiber: Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group ( P ＞ 0.05 ); The CSA of type Ⅱ fibers in VC group was markedly lower than control group ( P ＜ 0.05 ) .Conclusions Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.     

内脏高敏感大鼠白细胞介素-1β、肿瘤坏死因子α与5-羟色胺转运体的表达

目的 研究内脏高敏感大鼠结肠细胞因子和5-羟色胺(5-HT)转运体(SERT)的表达,为细胞因子和5-HT系统在内脏高敏感性产生机制中的作用提供依据.方法 16只胎龄小于8 d的新生SD大鼠被随机分为2组,每组8只.采用乳鼠醋酸灌肠法建立大鼠慢性内脏高敏感动物模型,以盐水灌肠作为对照组.待乳鼠成年后应用直肠内球囊扩张检测腹碓收缩阈值和弓背抬起阈值的方法评估其内脏敏感性;通过检测髓过氧化物酶(MPO)评价肠道黏膜炎症程度;采用免疫组化的方法检测大鼠结肠组织中IL-1β和TNFα的水平;采用Western blot方法检测大鼠结肠组织SERT的表达水平.结果 两组大鼠体重增长趋势基本一致,HE染色显示结肠黏膜未见明显急、慢性炎症改变;两组大鼠结肠组织MPO水平相比,差异无统计学意义[(0.497±0.570)U/g湿片比(0.623±0.739)U/g湿片,P=0.724];实验组大鼠腹壁收缩阈值和弓背抬起阈值分别为(0.19±0.06)ml和(0.47±0.13)ml,较对照组大鼠[(0.40±0.14)ml和(0.91±0.26)ml]显著减低,P＜0.01;实验组大鼠结肠IL-1β、TNFα的表达水平(0.196±0.002和0.194±0.001)均显著高于对照组(0.185±0.001和0.182±0.001),P＜0.01;实验组大鼠SERT蛋白相对表达水平(0.298±0.038)较对照组(0.634±0.200)显著减低,P＜0.05.结论 内脏高敏感大鼠IL-1β和TNFα的表达升高,SERT的表达水平减低,细胞因子与SERT可相互影响,IL-1β、TNFα和SERT可能在大鼠内脏高敏感性的发生机制中具有一定的作用.     

携带人B型利钠肽基因重组腺病毒对慢性心力衰竭大鼠心功能的影响

目的 观察外源基因人B型利钠肽对慢性心力衰竭(心衰)大鼠心功能的影响.方法 30只入选心衰大鼠,随机分为携带人B型利钠肽基因重组腺病毒组(Ad-hBNP组)、重组空白腺病毒组(Ad-Track组)、生理盐水组(NS组),另设不予任何治疗的假手术组作为对照;分别经腹腔注射予以相应治疗,每周1次,共4周.4周后实验动物行超声心动图、血流动力学检测,酶联免疫吸附试验检测血清外源基因人B型利钠肽水平,全心质量指数检测.结果 间断Ad-hBNP治疗后,Ad-hBNP组心衰大鼠室间隔厚度、左室后壁厚度、左室舒张末径、左室收缩末径[(2.34±0.29)mm、(2.28±0.18)mm、(6.50±0.42)mm、(3.54±0.59)mm]显著低于Ad-Track组[(2.71±0.35)mm、(3.02±0.85)mm、(7.71±0.83)mm、(4.72±0.80)mm,均为P＜0.05]和NS组[(2.78±0.23)mm、(2.83±0.53)mm、(7.34±0.97)mm、(4.55±0.77)mm,均为P＜0.05],而左室射血分数、左室短轴缩短率[(79.27±7.01)%、(43.38±6.73)%]显著高于Ad-Track组[(70.85±4.81)%、(35.72±3.68)%,均为P＜0.01]和NS组[(69.67±6.90)%、(34.91±5.10)%,均为P＜0.01].Ad-hBNP组与Ad-Track组和NS组比较:心率显著降低,左室收缩压显著升高[为(131.79±15.76)mm Hg(1 mm Hg=0.133 kPa)、(112.99±32.35)mm Hg、(117.13±15.26)mm Hg],左室内压最大上升速率显著升高[分别为(5037.20±430.41)mm Hg/s、(4217.40±1354.15)mm Hg/s、(4310.50±1293.97)mm Hg/s;P＜0.05];左室内压最大下降速率显著升高[分别为(-4382.00±1304.79)mm Hg/s、(-3725.00±791.34)mm Hg/s、(-3890.00±1043.73)mm Hg/s,均为P＜0.05];左室舒张末压降低[分别为(-4.24±4.00)mm Hg、(21.99±6.80)mm Hg、(18.00±12.25)mm Hg,均为P＜0.01];心脏质量及全心质量指数均降低.结论 间断给予Ad-hBNP能够有效地改善心衰大鼠心脏结构和功能.

Abstract：

Objective To evaluate the therapeutic effect of hBNP on rats with chronic heart failure (CHF). Methods Thirty CHF rats defined by echocardiography at 12 weeks post abdominal aortic constriction were randomly divided into Ad-hBNP group (2. 5 × 1010 VP/ml NS Ad-hBNP 1 ml/week ×4,n = 14), Ad-Track group ( n = 8 ), placebo group ( NS, n = 8 ), 10 sham-operated rats served as control group. After 4 weeks treatment, cardiac function was evaluated by echocardiography and hemodynamic measurements. Heart weight (HW) and HW/body weight (BW) ratio were determined. Results IVS,LVPW, LVEDD and LVESD were significantly reduced in the Ad-hBNP group [(2. 34 ±0. 29)mm, (2. 28 ± 0. 18)mm, (6. 50 ±0. 42)mm, (3.54 ±0. 59) mm] than those in the Ad-Track group[(2. 71 ±0. 35) mm,(3.02 ±0.85)mm, (7.71 ±0.83)mm, (4.72 ±0.80)mm] and in the NS group [(2.78 ±0.23)mm,(2. 83 ± 0. 53 ) mm, (7. 34 ± 0. 97 ) mm, (4. 55 ± 0. 77 ) mm, all P ＜ 0. 05]. The LVEF and LVFS of the Ad-hBNP group [(79. 27 ±7.01 )%, (43.38 ±6. 73)%] were significantly higher than in the Ad-Track group[(70.85±4.81)%, (35.72 ±3.68)%] and in the NS group[(69.67 ±6.90)%, (34.91 ±5.10)%, all P ＜0. 01]. HR[(417.48 ±32. 57) beats/min, (446. 85 ±61.49) beats/min, P ＜0. 05;(440. 83 ±32. 18) beats/min , P ＜0. 05], LVEDP[( - 4. 24 ±4. 00) mm Hg( 1 mm Hg =0. 133 kPa);(21.99 ±6. 80) mm Hg, P ＜0. 01; ( 18.00 ± 12. 25)mm Hg, P＜0. 01] were significantly decreased and while LVSP[(131.79 ±15.76) mm Hg; (112.99 ±32.35) mm Hg, P＜0.05; (117.13 ±15.26)mmHg], +dP/dtmax[(5037.20 ±430.41) mm Hg/s; (4217.40 ± 1354. 15)mm Hg/s, P ＜0.05;(4310. 50 ± 1293.97 ) mm Hg/s, P ＜ 0. 05] and - dP/dtmax [( - 4382. 00 ± 1304. 79 ) mm Hg/s;(-3725.00±791.34) mm Hg/s, P ＜ 0.05; ( - 3890.00 ± 1043.73) mm Hg/s, P ＜ 0.05] were significantly increased in Ad-hBNP group than in Ad-Track group and NS group ( all P ＜ 0. 05 ). HW and HW/BW were also decreased in Ad-hBNP group than in the Ad-Track group and the NS group. Conclusion Exogenous hBNP improved the cardiac function and attenuated remodeling in CHF rats.     

骨髓间充质干细胞移植对MRL/Ipr鼠B细胞活化因子及B细胞活化的影响

目的 探讨正常鼠骨髓问充质干细胞(BM-MSCs)移植对MRL/Ipr狼疮鼠B细胞活化因子(BAFF)表达及B细胞活化的影响.方法 18只雌性MRL/Ipr鼠随机分为MSCs治疗组和对照组,18周龄时治疗组经尾静脉移植MSCs 1×10~6/只;5只同周龄雌性BAL B/C小鼠作为健康阴性对照.酶联免疫吸附试验(ELISA)法检测血清BAFF、干扰素(IFN)-γ、白细胞介素(IL)-2、IL-10水平,流式细胞术检测脾脏中边缘区、T1期、T2期B细胞百分率及细胞数.结果 ①MSCs治疗8周后,治疗组血清BAFF水平[(32±14)ng/ml]显著低于对照组[(47±13)ng/ml](P＜0.05);血清IL-10[(19±7)pg/ml]显著低于对照组[(40±13)pg/ml](P＜0.01);血清IFN-γ、IL-2低于对照组[(26±20)pg/ml与(38±25)pg/ml、(73±10)pg/ml与(80±14)pg/ml],但差异无统计学意义.②MSCs治疗8周后,可降低治疗组脾脏边缘区B细胞百分率(15±4)%,对照组为(21±5)%,但差异无统计学意义,并能显著降低边缘区B细胞数[(9±6)×10~6与(19±10)×10~6,P＜0.05].③MSCs治疗8周后,可降低治疗组脾脏T1期、T2期B细胞百分率[(3.4±2.1)%与(7.3±4.0)%]、[(2.6±1.4)%与(4.8±2.7)%],但差异无统计学意义,并能显著降低T1期B细胞绝对数[(2.7±1.7)×10~6与(5.1±2.0)×10~6,P＜0.05]、T2期B细胞绝对数[(2.0±1.2)×10~6与(3.7±1.7)×10~6,P＜0.05].结论 BM-MSCs移植可能通过抑制体内BAFF的过量表达,进而抑制狼疮鼠B细胞的过度活化.     

良性前列腺增生与肥胖相关性研究

目的 探讨良性前列腺增生(BPH)与肥胖或中心性肥胖的关系.方法 选择老年男性患者109例,分为BPH组(59例)和非BPH组(50例),检测血清前列腺特异性抗原(PSA)及性激素、血脂等相关生化指标;测量身高、体质量、腰围等物理指标;经腹超声测量前列腺体积,并随访至少3次.结果 肥胖组BPH患病率(73.33%)及超体质量组BPH患病率(64.28%)均较正常组(26.67%)增高(x2分别为13.991,6.836,均P＜0.002),中心性肥胖组BPH患病率(71.19%)较非中心性肥胖组(36.00%)明显增高(x2=12.156,P＜0.001);BPH组腰围身高指数、腰围、体质量、体质指数、臀围[0.56±0.05、(93.6±8.8)cm、(72.6±9.7)kg、(25.7±3.4)kg/m2和(100.2±6.6)cm]明显高于非前列腺增生组[0.52±0.06、(87.0±10.1)cm、(64.5±9.3)kg、(23.1±2.9)kg/m2和(95.6±8.1)cm](t分别=-3.30,-3.65,-4.38,-4.17,-3.18,均P＜0.01);肥胖组前列腺总体积高于正常组[(40.8±23.5)ml与(20.1±6.1)ml,t=-2.82,P＜0.01),中心性肥胖组明显高于非中心性肥胖组[(42.8±25.6)ml与(26.9±11.2)ml],(t=-3.93,P＜0.001);中心性肥胖组雌二醇/总睾酮(E2/TT)比值、胰岛素抵抗指数(HOMA-IR)(9.06±4.36、2.81±2.80)高于非中心性肥胖组(7.38±3.11、1.55±0.76)(t分别=-2.02,-4.24,均P＜0.05),血清TT、性激素结合蛋白(SHBG)则低于非中心性肥胖组[(4.54±1.54)nmol/L对(5.20±1.54)nmol/L,(45.8±17.24)nmol/L对(59.6±26.09)nmol/L,均t分别=2.16,2.79,P＜0.05];Logistic逐步回归分析表明,腰围是影响前列腺体积的主要因素(x2=19.52,P=0.000);前列腺总体积的年增长率在肥胖组同样高于正常组[(7.14±8.09)ml与(1.49±5.14)ml,t=-2.19,P＜0.05],在中心性肥胖组明显高于非中心性肥胖组[(7.96±13.81)ml与(1.35±5.36)m1,t=-3.28,P＜0.01];中心性肥胖组的前列腺特异性抗原密度(PSAD)低于非中心性肥胖组(0.048±0.036对0.090±0.093,t=2.02,P＜0.05);肥胖组的PSAD低于正常组(0.052±0.039与0.091±0.080,t=3.13,P＜0.01).结论 BPH的发生与肥胖,尤其是中心性肥胖密切相关,其机制可能与肥胖患者体内性激素失衡、生长激素-胰岛素样生长因子轴的紊乱有关.

Abstract：

Objective To explore the relationship between benign prostatic hyperplasia (BPH)and obesity. Methods The 109 elder men were divided into two groups: BPH group (n=59) and non-BPH group (n= 50). The blood samples were collected for the detections of prostate specific antigen (PSA), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), insulin,androgen, estrogen, sex hormone binding globulin (SHBG) and dehydroepiandrosterone(DHEA).The anthropometric indexes including height, body weigh, waist circumference (WC), hip circumference (HC), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) were measured and calculated. The total prostate volume (TPV) were measured by transabdominal ultrasonography three times at least. Results The morbidity rate of BPH was significantly higher in obesity group and over weight group than in health control group (73.33% and 64.28% vs. 26. 67%, x2 = 13. 991 and 6. 836, both P＜0. 002). So was in central obesity group versus in health control group (71.19% vs.36.00%, x2 =12. 156, P＜0. 001). The waist-height index, waist circumference, body weight, BMI and hip circumference were significantly higher in BPH group than in non-BPH group [(0. 56±0. 05)vs. (0.52±0.06), (93. 6±8.8) cm vs. (87.0± 10. 1) cm; (72.6±9.7) kg vs. (64.5±9.3) kg;(25.7±3.4) kg/m2 vs. (23.1±2.9) kg/m2; (100.2±6.6) cm vs. (95.6±8. 1) cm; t=-3.3, -3. 65, -4.38, -4. 17 and -3.18, respectively, all P＜0.01]. The TPV was higher in obesity groupthan in normal group [ (40.8± 23.5 ) ml vs. (20. 1 ± 6.1 ) ml, t = - 2.82, P＜ 0. 002] and obviously higher in central obesity group than in non-central obesity group [(42.8±25.6)ml vs. (26. 9±11.2)ml, t= -3. 93, P＜0. 001]. The ratio of E2/TT and HOMA-IR were higher in central obesity group [(9. 06±4.36) and (2.81 ±2. 80)] than in non-central obesity group [(7. 38±3. 11) and (1. 55±0.76), t= -2.02 and -4.24, both P＜0. 05]. Inversely, the TT and SHBG were lower in central obesity group than in non-central obesity group [(4.54 ± 1.54) nmol/L vs. (5.20 ± 1.54) nmol/L,(45.8± 17.24) nmol/L vs. (59.6 ± 26.09) nmol/L, t = 2.16 and 2.79, both P＜ 0. 05]. Logistic regression analysis showed that waist circumference was a major factor affecting TPV (x2= 19.52, P=0. 000). The annual growth rate of TPV was significantly higher in obesity group and central obesity group than in health control group [(7. 14±8. 09)ml vs. (1. 49±5.14)ml, (7. 96±13.81)mlvs. (1. 35±5.36)ml, t=-2.19 and -3.28, both P＜0. 05]; The PSAD was significantly lower in central obesity group than in health control group [(0. 048±0. 036) vs. (0. 090±0. 093), t=2.02, P＜0. 05], and lower in obesity group than in health control group [(0. 052 ±0. 039) vs. (0. 091 ±0. 080), t= 3. 13, P＜0. 01]. Conclusions The occurrence of BPH is closely related to obesity,especially central obesity. Its mechanism may be related to sex hormone imbalance and the GH/IGF-1 axis disorders in obese patients.     

表皮生长因子受体对支气管哮喘大鼠气道炎症的影响

目的 探讨表皮生长因子受体(EGFR)在支气管哮喘(简称哮喘)大鼠急慢性气道炎症的作用以及阻断EGFR的激活对气道炎症的影响.方法 将45只sD大鼠按随机数字表法分为对照组(A1、A2、A4组)、哮喘组(B1±、B2、B4组)和治疗组(C1、C2、C4组),每组5只,其中1、2和4分别表示激发1、2和4周.治疗组在每次卵清白蛋白激发前1 h给予酪氨酸激酶抑制剂(TKI)金雀异黄素(genistein)20 mg/kg腹腔注射.末次激发后收集BALF行细胞总数及分类计数.肺组织HE染色并行气道黏膜下炎症评分.免疫组织化学及免疫荧光染色观察气道上皮EGFR表达及其酪氨酸磷酸化(活化的ECFR)程度.两组数据间的比较采用单因索方差分析,多组间比较采用g检验.结果 (1)B组各时段BALF中细胞总数及各类细胞绝对计数均高于A组相应时段组(均P<0.05),嗜酸粒细胞在2周末达高峰;C组各时段BALF中细胞总数[分别为(48±6)、(51±9)和(57±12)×105]及嗜酸粒细胞计数[分别为(2.5±0.5)、(2.7±0.6)和(2.6±0.5)×105]均低于相应B时段组[细胞总数分别为(70±10)、(88±8)和(72±10)×105>,嗜酸粒细胞数分别为(5.6±0.8)×105、(6.6±0.6)×105和(4.3±0.4)×105],差异有统计学意义(均P<0.05);C组各时段BALF中中性粒细胞及淋巴细胞计数与相应时段B组比较差异无统计学意义;C1组BALF中上皮细胞数[(2.5±0.5)×105]低于B1组[(4.9±0.7)×103](q=4.671,P<0.05),C4组BALF中上皮细胞数[(5.7±1.2)×105]高于B4组[(4.3±0.4)×105](q=4.012,P<0.05).(2)C4组气道黏膜下炎症评分(3.6±0.6)低于B4组(5.1±0.6)(q=4.923,P<0.05).(3)B组各时段各级气道EGFR蛋白表达均高于相应时段A组(均P<0.01);气道上皮EGFR活化程度A组分别为(1.84±0.26)、(1.43±0.29)和(1.67±0.32),B组分别为(3.69±0.43)、(3.57±0.29)和(4.46±0.47),C组分别为(3.12±0.24)、(3.00±0.28)和(2.69±0.54),B组各时段气道上皮EGFR活化程度均高于相应时段A组(均P<0.05);C组各时段气道上皮EGFR活化程度均弱于相应时段B组(均P<0.05).(4)相关分析显示气道上皮EGFR表达及其活化程度均与BALF中细胞总数、嗜酸粒细胞、中性粒细胞及淋巴细胞绝对计数,以及气道炎症评分呈明显正相关.结论 哮喘大鼠气道上皮EGFR参与气道炎症,TKI金雀异黄素有一定抑制哮喘大鼠急慢性气道炎症的作用.     

晚期糖基化终末产物受体在急性坏死性胰腺炎大鼠中的表达

目的 观察急性坏死性胰腺炎(ANP)大鼠发病过程中胰腺组织及血清中晚期糖基化终末产物受体(the receptor for advanced glycation end products,RAGE)含量变化的规律.方法 64只雄性SD大鼠按完全随机法分为对照组,ANP 6、18、24、36、48、72、96 h组,每组8只.采用腹腔注射20％L-精氨酸250 mg/100 g体重2次、间隔1h方法制备ANP模型.对照组大鼠腹腔注射等容积生理盐水.胰腺组织行病理学检查并评分.检测腹水量、血清淀粉酶及RAGE浓度,实时PCR法检测胰腺组织RAGE mRNA表达.结果 ANP组胰腺病理损伤随时间延长逐渐加重;腹水量从6h的(1.98±0.64)ml增加到96h的(8.69 ±0.62) ml;血清淀粉酶浓度从造模后6h开始升高,18h达(5069.88±603.25)U/L,36 h时恢复正常.对照组大鼠血清RAGE浓度及胰腺组织RAGE mRNA表达量分别为(18.33±2.99) ng/ml和0.41 ±0.13.ANP组6h时两者开始升高,分别为(30.31±5.03)ng/ml和1.57±0.19,较对照组显著升高(P＜0.05);24 h组达峰值,分别为(105.41±21.31)ng/ml和4.23±0.73,较ANP其他时间点显著升高(P值均＜0.05);96 h下降至最低点,分别为(33.54±6.96) ng/ml和1.19±0.19,但仍高于对照组(P＜0.05).结论 血清RAGE浓度及胰腺组织RAGE mRNA表达量在ANP发生36 h内逐渐增加,随后下降,但始终高于正常值.     

电压门控钙通道在三硝基苯磺酸诱导的炎症性内脏高敏中作用机制的研究

目的 研究炎症性内脏高敏大鼠背根神经节(DRG)基因表达的变化及电压门控钙离子通道(VGCC)在炎症性内脏高敏感性中的作用.方法 雄性清洁级SD大鼠180只,体重200～300 g,三硝基苯磺酸(TNBS)模型组(n=90)缓慢注入2.0%TNBS,剂量为100 mg/kg;正常对照组(n=90)仅灌注等量0.9%氯化钠溶液.造模后第4天,大鼠的cDNA表达谱基因芯片检测大鼠1.6S2节段DRG基因表达谱变化.通过实时定量逆转录聚合酶链反应(RT-PCR)和Western印迹检测进行验证.胞内钙检测及全细胞膜片钳记录分析胞内钙及电压门控钙电流变化.另取SD大鼠54只,均分为6组,分别予以TNBS造模及脊髓鞘内给予特异性钙通道阻滞剂,观察大鼠内脏敏感性的变化.腹部撤离反射(AWR)检测大鼠内脏敏感性.结果 TNBS模型组L6～s2节段DRG172个基因的表达出现显著变化,包括离子通道、膜受体及胞内第二信使等.其中,L-型钙通道(Cav 1.2)和R-型钙通道(Cav2.3)显著上调,RT-PCR及Western印迹检测结果均验证了芯片结果.胞内钙检测显示,TNBS模型组结肠特异感觉神经元的静息胞内钙含量与正常对照组相比差异无统计学意义(P＞0.05);而胞内钙瞬变量较正常对照组显著增加(P＜0.05).全细胞膜片钳记录显示TNBS模型组结肠初级感觉神经元L-型和R-型钙电流较正常对照组明显增加(P＜0.05).脊髓鞘内给予尼莫地平和SNX-482后可显著降低炎症性内脏高敏大鼠的内脏敏感性(P＜0.05).结论 Cav1.2和Cav2.3表达的上调在炎症性内脏高敏中起了非常重要的作用,很可能是炎症性内脏高敏治疗的潜在靶点.

Abstract：

Objective To screen the difference of gene expression in dorsal root ganglia (DRG)of inflammatory visceral hypersensitivity rats and to explore the role of voltage gated calcium channel (VGCC) in inflammatory visceral hypersensitivity. Methods Total 180 male Sprague-Dawley rats were in this study,the weight varied from 200 gram to 300 gram. 2,4,6-trinitrobenzenesulfonic acid (TNBS) model group was maken by 2. 0% TNBS slowly injection,the dosage was 100mg per kilogram. The normal control group was only injected with same volume of 0. 9% sodium chloride solution. After the model had been maken for four days,gene expression profiles of L6-S2 DRGs were tested by rat cDNA microarray chips. And the result was verified by RT-PCR and Western blot. The changes of intracellular Ca2+ and the voltage gated calcium currents were recorded by patch-clamp.The special Ca2+ channel blockers were given by intrathecal injection,and then the changes of visceral sensitivity were observed. The visceral sensitivity was measured by abdominal withdrawal reflex (AWR). Results There were significant changes of 172 genes expression in L6-S2 DRGs of TNBS model rats,which included Ca2+ channel,membrane receptor and intracellular second messenger. Of those,L-type Ca2+ channel (Cav1. 2) and R-type Ca2+ channel (Cav2. 3) were significantly up-regulated. The results of gene microarray chips were further confirmed by RT-PCR and Western blot.The intracellular Ca2+ testing indicated that there was no statistical significant of resting intracellular Ca2+ in colonic special sensory neuron between TNBS group and normal control group (P＞0. 05);while the evoked transients [Ca2+] significantly increased compared with normal control group (P＜0. 05). The whole cell patch clamp recording showed that the L-type and R-type calcium current were significantly increased in colonic primary sensory neurons of TNBS group compared with normal control group (P＜0. 05). The inflammatory visceral hypersensitivity was significantly reduced by intrathecal injection of nimodipine and SNX-482 (P＜0. 05). Conclusion The up-regulation of Cav1. 2and Cav2. 3 play an important role in inflammatory visceral hyperalgesia,which may be the possible potential therapeutic targets for visceral inflammatory hyperalgesia.     

神经生长因子及其高亲和力受体在慢性阻塞性肺疾病患者细支气管上皮细胞中的表达

目的 探讨神经生长因子和酪氨酸激酶A在COPD患者细支气管上皮细胞中的表达.方法 选取同济医学院附属同济医院胸外科2008年1-6月因肺肿瘤行肺叶或全肺切除术患者31例为研究对象,分为吸烟合并COPD组11例,均为男性,年龄42～79岁,平均(61±11)岁;吸烟无COPD组11例,均为男性,年龄45～67岁,平均(56±6)岁;对照组9例,其中女7例,男2例,年龄38～68岁,平均(52±10)岁.取石蜡包埋的非肿瘤病灶病理组织切片,采用免疫组织化学SP法检测神经生长因子和酪氨酸激酶A在细支气管上皮细胞中的表达水平.组间差异采用方差分析及q检验,采用Person法进行相关性分析.结果 吸烟合并COPD组细支气管上皮细胞中神经生长因子和酪氨酸激酶A阳性表达率分别为(41±11)/mm和(45±4)/mm,均明显高于吸烟无COPD组[(28±9)/mm和(20±3)/mm]及对照组[(24±6)/mm和(17±6)/mm],差异均有统计学意义(q值为4.83～7.24,均P＜0.05);神经生长因子与酪氨酸激酶A的阳性表达率均呈显著正相关(r=0.655,P＜0.05);神经生长因子和酪氨酸激酶A的阳性表达率与FEV1/FVC呈显著负相关(r值分别为-0.486和-0.665;均P＜0.05),与吸烟指数无相关性(r值分别为0.282和0.470,均P＞0.05).结论 神经生长因子和酪氨酸激酶A在COPD患者细支气管上皮细胞中的表达增强,提示其与COPD的疾病进展有关.

Abstract：

Objective To study the expressions of nerve growth factor (NGF) and tyrosine kinase receptor A (TrkA) in bronchiolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). Methods Thirty-one patients admitted to Tongji Hospital from January to June in 2008 for incision of lung tissues were included in the study They were divided into 3 groups: ( 1 ) the control goup:9 patients (2 females and 7 males), average age (52 ± 10) years old, who did not smoke and did not have COPD; (2) the COPD group: 11 patients, all male, average age (61 ± 11 ) years old, who smoked and had a diagnosis of COPD; (3) the smoker group, 11 patients, all male, average age ( 56 ± 6) years old, who smoked but did not have COPD. The pathological changes were detected by HE staining. The localizations and the levels of NGF and TrkA expressions in bronchiolar epithelial cells were observed by immunohistochemical technology on bronchiolar biopsy sections. The analysis of variance ( ANOVA), the student-Newman-Keuls (SNK) and the Pearson correlation coefficient were used for statistical analysis through SPSS13.0. Results The COPD group exhibited significantly enhanced NGF and TrkA expression levels, and the positive cell numbers were (41 ± 11 )/mm and (45 ± 4)/mm in bronchiolar epithelial cells respectively, as compared with the other 2 groups [(28 ± 9)/mm, (20 ± 3)/mm and (24 ±6)/mm, (17 ± 6)/mm], q=4. 83 -7.24, all P ＜ 0. 05. A significant positive correlation was found between the expressions of NGF and TrkA in bronchiolar epithelial cells ( r = 0. 655, all P ＜ 0. 05 ＝. A significant negative correlation was found between NGF and TrkA expressions and the levels of FEV1/FVC ( r =- 0. 486, - 0. 665, all P ＜ 0. 05 ＝. Conclusions The expressions of both NGF and TrkA in bronchiolar epithelial cells were significantly increased in COPD patients. It suggested that NGF and TrkA might play an important role in the progress of COPD.     

短期胰岛素泵强化治疗对初发2型糖尿病患者血浆vaspin水平的影响

目的 观察短期胰岛素泵强化治疗对初发2型糖尿病患者血浆内脏脂肪组织来源的丝氨酸蛋白酶抑制物vaspin水平的影响,探讨其与胰岛素敏感性的关系.方法 30例初发2型糖尿病患者使用胰岛素泵强化治疗2周,治疗前后采用高胰岛素-正葡萄糖钳夹术评价其胰岛素敏感性,用酶免法测定血浆vaspin及相关代谢指标.结果 2型糖尿病组空腹血浆vaspin水平高于正常糖耐量(NGT)组和糖调节受损(IGR)组.2型糖尿病组经胰岛素泵强化治疗后葡萄糖代谢率升高[(5.10±0.51对2.99±0.42)mg·kg-1·min-1,P＜0.05],稳态模型评估的胰岛素抵抗指数(HOMA-IR)降低[2.30(1.09～7.20)对4.28(1.70～6.47),P＜0.05],同时血浆vaspin水平也显著降低[(1.19±0.57对1.83±0.55)ng/ml,P＜0.05],且vaspin水平的降低与HOMA-IR的改变呈明显正相关.结论 胰岛素泵强化治疗能有效改善2型糖尿病患者的胰岛素敏感性,降低血浆vaspin水平;且血浆vaspin水平与2型糖尿病患者胰岛索敏感性有关.     

依达拉奉对急性脑梗死患者自由基清除的临床研究

目的 探讨依达拉奉清除自由基治疗急性脑梗死的临床疗效.方法 脑梗死患者60例,随机分为治疗组和对照组,两组均常规脱水、降颅压、控制血压等,治疗组用生理盐水250 ml+依达拉奉30 mg静脉滴注,2次/d,连续使用14 d;对照组用生理盐水250 ml,静脉滴注,2次/d,连续使用14d.两组分别于治疗前和治疗后第14 d进行神经功能缺失程度和日常生活活动能力评分(ADL),测定血清超氧化物歧化酶(SOD).结果 治疗组与对照组比较,治疗第14天患者的神经功能缺失程度[(7.5±5.4)分与(15.9±7.9)分,P＜0.05]、ADL得分[(58.32±11.57)分与(43.73±12.48)分,P＜0.05]和血清SOD[(157.25±21.81)mmol/L与(127.08±13.14)mmol/L,P＜0.05]都得到改善,差异均有统计学意义.结论 依达拉奉治疗急性脑梗死可以提高机体清除自由基能力,促进神经功能恢复.