罗非昔布对单侧输尿管梗阻大鼠肾间质纤维化的改善作用

目的:观察选择性环氧合酶-2抑制剂罗非昔布对单侧输尿管梗阻大鼠肾间质纤维化的改善作用.方法:24只Wistar大鼠随机分成对照组(C组)、单侧输尿管梗阻(UUO)手术组(U组)及罗非昔布治疗组(R组),每组8只.U组和R组制作UUO模型,C组为假手术对照组.术前24 h及术后以灌胃方式给药,R组给予罗非昔布(10 mg·kg-1·d-1),C组和U组给予等量生理盐水,1次/d,共2周.放射免疫法测定尿TXB2浓度.免疫组化方法检测术后2周肾组织中TGF-β1、COX-2的表达,并用硝酸还原酶法测定肾皮质组织中NO含量.结果:与C组相比,U组及R组尿TXB2水平、COX-2、TGF-β1表达、NO含量均增高(P＜0.05),与U组相比,R组尿TXB2水平、COX-2、TGF-β1表达、NO含量均降低(P＜0.05).结论:罗非昔布可通过抑制COX-2活性、下调TGF-β1的表达,抑制NO的合成等,从而延缓UUO大鼠肾间质纤维化的进展.     

选择性环氧化酶2抑制剂对梗阻性肾病大鼠肾组织中核因子кB和转化生长因子β_1的调节

目的:探讨塞来昔布与吲哚美辛比较对单侧输尿管梗阻(UUO)大鼠模型肾脏的保护作用及可能机制。方法:将塞来昔布和吲哚美辛应用于UUO大鼠,4周后测定血清肌酐及尿素氮水平,放射免疫法测定大鼠尿液血栓烷素B(2TXB2)浓度,免疫组化法检测肾脏核因子кB(NF-кB)和转化生长因子β(1TGF-β1)的表达。结果:塞来昔布及吲哚美辛均降低尿TXB2浓度,塞来昔布组更为显著;与对照组相比,其余3组NF-кB及TGF-β1的蛋白表达水平均显著上升,肾间质纤维化严重;塞来昔布治疗后,上述蛋白表达水平显著下调,肾间质纤维化程度明显减轻。结论:塞来昔布能减轻UUO大鼠肾间质纤维化,下调NF-кB的表达,减少肾间质单核巨噬细胞浸润可能是其机制之一。     

选择性环氧化酶2抑制剂对梗阻性肾病大鼠肾组织中核因子κB和转化生长因子β1的调节

目的：探讨塞来昔布与吲哚美辛比较对单侧输尿管梗阻（UUO）大鼠模型肾脏的保护作用及可能机制。方法：将塞来昔布和吲哚美辛应用于UUO大鼠，4周后测定血清肌酐及尿素氮水平，放射免疫法测定大鼠尿液血栓烷素B2（TXB2）浓度，免疫组化法检测肾脏核因子κB（NF-κB）和转化生长因子β1（TGF-β1）的表达。结果：塞来昔布及吲哚美辛均降低尿TXB2浓度，塞来昔布组更为显著；与对照组相比，其余3组NF-κB及TGF-β1的蛋白表达水平均显著上升，肾间质纤维化严重；塞来昔布治疗后，上述蛋白表达水平显著下调，肾间质纤维化程度明显减轻。结论：塞来昔布能减轻UUO大鼠肾间质纤维化，下调NF-κB的表达，减少肾间质单核巨噬细胞浸润可能是其机制之一。     

大蒜素对大鼠肾间质纤维化干预作用及对肾组织TGF-β1/Smads信号通路的影响

目的观察大蒜素对大鼠肾间质纤维化的干预作用,探讨其与TGF-β1/Smads信号通路的关系。方法 18只SD雄性大鼠随机分为假手术组、模型组和大蒜素组,每组6只,采用单侧输尿管结扎术(UUO)建立大鼠肾间质纤维化模型,造模后第1天大蒜素组大鼠予大蒜素60mg·kg~(-1)·d~(-1)灌胃,假手术组和模型组大鼠予等量生理盐水灌胃。造模后第15天称量大鼠体质量及左肾质量,计算肾脏指数,检测三组大鼠血清肌酐(SCr)、尿素氮(BUN)及24h尿蛋白(U-TP),并处死大鼠,摘取肾组织,包埋切片后行Masson染色,观察肾组织病理结构,运用免疫组化法检测大鼠肾组织转化生长因子-β1(TGF-β1)及α-平滑肌肌动蛋白(α-SMA)表达,Western Blot法测定肾组织磷酸化信号转导分子2(p-Smad2)和磷酸化信号转导分子3(p-Smad3)表达。结果与模型组比较,造模后第15天大蒜素组大鼠体质量显著增高[(298.52±14.82)g比(275.53±23.92)g,P0.05],肾脏指数显著下降[(0.53±0.15)%比(0.84±0.25)%,P0.01],肾脏组织病变程度有所改善,血SCr、BUN及U-TP均显著低于模型组[SCr:(48.54±5.03)μmol/L比(55.10±7.50)μmol/L;BUN:(5.56±0.43)mmol/L比(6.25±0.51)mmol/L;U-TP:(1009.87±105.02)mg/L比(1300.57±229.65)mg/L,P0.05或P0.01],肾组织TGF-β1、α-SMA、p-Smad2和p-Smad3蛋白表达量均有下调[TGF-β1:(0.227±0.011)比(0.282±0.020);α-SMA:(0.326±0.009)比(0.471±0.012);p-Smad2:(0.195±0.011)比(0.279±0.016),p-Smad3:(0.220±0.020)比(0.699±0.076),P均0.01]。结论大蒜素可能通过调节TGF-β1/Smads信号通路,改善大鼠肾间质纤维化程度,对肾功能起到一定的保护作用。     

选择性环氧化酶-2抑制剂对梗阻性肾病大鼠肾组织中巨噬细胞趋化蛋白-1的调节

目的 探讨塞来昔布(celecoxib)与吲哚美辛(indomethacin)比较对单侧榆尿管梗阻(UUO)大鼠模型肾脏的保护作用及可能机制.方法 大鼠随机分为4组:模型组(UUO组),塞来昔布治疗组(UUO+celecoxib组),吲哚美辛治疗组(UUO+indomethacin组)和假手术组即对照组(SOR).4周后检测各组大鼠血清肌酐及尿素氮水平,并采用放射免疫方法 测定大鼠尿液血栓烷素B2(TXB2)浓度.应用免疫组织化学方法 检测肾脏巨噬细胞趋化蛋白-1(MCP-1)、转化生长因子-β,(TGF-β1)及Ⅳ型胶原(ColIV)的蛋白水平.结果 塞来昔布及吲哚美辛均可以降低尿TXB2浓度,以塞来昔布组更为显著;与对照组相比,其余3组,MCP-1、TGF-β;及ColⅣ的蛋白表达水平均显著上升,肾间质纤维化严重;塞来昔布治疗后,上述蛋白表达水平显著下调,肾间质纤维化程度明显减轻.结论 塞来昔布能减轻UUO大鼠肾间质纤维化,下调MCP-1的表达,减少肾间质单核巨噬细胞浸润可能是其机制之一.     

冬虫夏草对梗阻性肾病大鼠肾间质表皮生长因子及转化生长因子-β1表达的影响

目的探讨冬虫夏草对单侧输尿管梗阻大鼠肾间质纤维化的防治作用及可能机制。方法将大鼠分成3组:假手术组(SOR组)、单侧输尿管梗阻手术组(UUO组)和冬虫夏草治疗组(CST组)。无菌条件下UUO组及CST组均进行左侧输尿管结扎手术,而SOR组仅分离左侧输尿管但不结扎及剪断输尿管。于手术当天开始CST组予冬虫夏草菌粉,SOR组及UUO组予蒸馏水,均每天一次性灌胃。于术后第7、14、21、28天分别检测血尿素氮、血肌酐;梗阻肾组织行HE染色,ELISA测定表皮生长因子-β1(EGF)及Western blot检测转化生长因子-β1(TGF-β1)的表达。结果 3组大鼠的血尿素氮、血肌酐值于各时间点的差异无统计学意义(P>0.05);CST组HE染色见肾间质纤维化程度较UUO组减轻;CST组肾组织TGF-β1的表达明显低于UUO组(P<0.05),EGF的表达明显高于UUO组(P<0.05)。结论冬虫夏草可能通过调节TGF-β1及EGF的表达而减轻输尿管梗阻引起的肾间质纤维化。     

黄芪多糖配伍三七总皂苷对糖尿病模型大鼠肾脏保护作用研究

目的探讨黄芪多糖与三七总皂苷配伍对糖尿病大鼠肾脏功能的保护作用。方法 SPF级SD大鼠60只,10只为正常对照组,50只予腹腔注射链脲佐菌素建立糖尿病大鼠模型,将糖尿病模型大鼠随机分为模型组、黄芪多糖组、三七总皂苷组、黄芪多糖与三七总皂苷配伍组、贝那普利组,每天给相应药物1次,连续8周。8周后测定各组大鼠24h尿总蛋白、血糖、血肌酐和尿素氮;取肾脏进行病理组织学检查。结果与正常对照组比较,模型组大鼠24h尿总蛋白[(103.76±4.67)mg/24h比(13.82±4.49)mg/24h]、血糖[(28.44±3.74)mmol/L比(6.59±1.11)mmol/h]、血肌酐[(111.91±9.46)μmol/L比(44.78±4.12)μmol/L]和尿素氮[(10.90±1.76)mmol/h比(5.53±1.27)mmol/L]显著升高(P0.01);病理组织学检查可见模型组大鼠肾小球基底膜增厚,肾小管出现大量炎症细胞浸润,间质纤维化;与模型组比较,黄芪多糖组大鼠尿蛋白[(84.01±7.20)mg/24h]、血糖[(20.60±2.10)mmol/L]和肌酐[(80.58±4.52)μmol/L]明显下降(P0.05);三七总皂苷组大鼠血糖[(21.86±4.08)mmol/L]和肌酐[(77.79±5.59)μmol/L]下降(P0.05);黄芪多糖和三七总皂苷配伍组大鼠尿蛋白[(66.00±3.43)mg/24h]、血糖[(16.34±2.34)mmol/L]、肌酐[(68.94±3.22)μmol/L]和尿素氮[(7.43±1.48)mmol/L]含量均明显下降(P0.01)。各给药组肾脏病理改变均有不同程度改善。结论黄芪多糖与三七总皂苷配伍对糖尿病大鼠的肾脏具有保护作用,其作用优于黄芪多糖和三七总皂苷单用组。     

尿毒清颗粒对单侧输尿管梗阻肾间质纤维化大鼠肾脏Toll样受体4表达的影响

目的观察尿毒清颗粒对单侧输尿管梗阻模型大鼠肾组织Toll样受体4(TLR4)表达的影响,探讨TLR4在导致肾间质纤维化中的作用。方法将24只大鼠随机分为正常对照组、假手术组、手术组和尿毒清组,每组6只。14 d后处死大鼠,检测各组大鼠的肾功能及总超氧化物歧化酶(T-SOD)活力、丙二醛(MDA)水平。采用反转录聚合酶链反应(RT-PCR)检测转化生长因子-β1(TGF-β1)mRNA的表达水平。采用免疫组化半定量法分析TLR4表达,并观察肾脏病理变化。结果 4组大鼠尿素氮(BUN)、血肌酐(SCr)、T-SOD、MDA水平比较,差异均有统计学意义(P<0.01);4组大鼠TGF-β1mRNA和TLR4的表达水平比较,差异均有统计学意义(P<0.01)。其中,假手术组与手术组、手术组与尿毒清组的TGF-β1mRNA和TLR4表达水平比较,差异均有统计学意义(P<0.05)。结论单侧输尿管梗阻可以诱导大鼠肾间质纤维化,氧化应激可能通过TLR4途径参与肾间质纤维化的形成,尿毒清治疗可明显改善大鼠的肾间质纤维化程度。     

帕瑞昔布对输尿管梗阻后肾功能的保护作用

目的:探讨选择性COX-2抑制剂帕瑞昔布对大鼠双侧输尿管梗阻(BUO)后肾功能的保护作用。方法:将大鼠随机分为BUO组、给药组和对照组,给予帕瑞昔布或生理盐水灌胃。BUO组和给药组手术结扎输尿管,对照组不结扎。术后24h采血并取出双肾,测定血浆中的钠、钾、肌酐和尿素值,并对肾组织进行免疫组织化学染色。结果:大鼠双侧输尿管梗阻术后24h肾组织中COX-2的表达显著增加,而双侧输尿管梗阻后使用帕瑞昔布的大鼠,肾组织中COX-2的表达显著减弱,反映肾功能的各项血浆生化指标改变亦显著减轻。结论:选择性COX-2抑制剂帕瑞昔布对大鼠输尿管梗阻所致肾功能损伤具有一定的保护作用。     

罗格列酮联合替米沙坦对单侧输尿管梗阻大鼠慢性肾纤维化的改善作用

[目的]观察罗格列酮、替米沙坦单用及联合使用对单侧输尿管梗阻（UUO）大鼠肾脏纤维化的作用。[方法]大鼠随机分成5组,即假手术组、模型组、罗格列酮干预组、替米沙坦干预组、联合用药组。术后14 d处死,RT-PCR方法检测肾皮质TGF-β1及TIMP？1 mRNA的表达,Western blotting方法检测肾皮质中MMP-9蛋白的表达。[结果]罗格列酮、替米沙坦单用都可减轻UUO模型大鼠肾脏TGF-β1和TIMP-1高表达;二者联合应用时,肾组织TGF-β1和TIMP-1表达下降更有显著性意义（P〈0.05）。罗格列酮、替米沙坦单用或联合应用对UUO模型大鼠肾组织MMP-9表达无明显影响（P〉0.05）。[结论]罗格列酮、替米沙坦均可下调TGF-β1的表达,纠正MMP-9/TIMP-l的失衡。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.