缺血预处理对糖尿病大鼠心肌梗死和细胞因子的影响

目的 观察大鼠心肌梗死面积和细胞相关因子的变化,探讨缺血预处理（IP）对缺血－再灌注（I／R）糖尿病大鼠心肌的保护作用。方法 向健康SD大鼠腹腔内注射链脲佐菌素（每只60mg/kg）制造糖尿病大鼠模型。2d后测定血糖,将血糖≥11．1mmol/L定为糖尿病鼠,共39只。2周后,麻醉大鼠。开胸结扎冠状动脉左前降支（LADCA）复制IP和I／R模型。将39只糖尿病大鼠分为IP组、非缺血预处理（NIP）组、对照组,每组13只。记录Ⅱ导联心电图,测定心腔血清肌酸激酶同工酶（CK－MB）、白细胞介素－8（IL－8）、肿瘤坏死因子α（TNFα）、心肌组织丙二醛（MDA）、超氧化物歧化酶（SOD）含量。取心脏切片染色,计算心肌缺血范围和心肌坏死范围。结果 IP组和NIP组间心肌缺血范围分别为46．6％和48．6％,无显著性差异,心肌坏死范围分别为64．8％和32．6％9P＜0．01）。IP组再灌注期室性心律失常减少,尤其是室颤较NIP组显著减少52．9％（P＜0．01）。IP组CK－MB和TNFα及MDA显著低于NIP组（P＜0．05）。结论 缺血预处理可通过减少TNFα和抗氧化作用,减少心肌坏死范围和降低糖尿病大鼠室颤的发生,从而减轻糖尿病大鼠心肌I／R的严重损害。     

缺血预适应对糖尿病大鼠再灌注心肌的保护作用

目的　通过建立大鼠缺血预适应 (IP)模型 ,探讨IP对缺血 再灌注 (I/P)糖尿病大鼠心肌的保护作用。方法　在SD大鼠腹腔内注射链佐星 (6 0mg/kg)制造糖尿病大鼠模型。 2d后 ,随机时刻测定血糖 ,将血糖≥ 11.1mmol/L定为糖尿病大鼠 2 2只 ,另外 2 2只血糖正常鼠为非糖尿病鼠。 2周后 ,麻醉大鼠 ,结扎和放松冠状动脉左前降支(LAD)复制IP和I/P模型。将 44只大鼠分为IP糖尿病大鼠组 (DIP组 )、IP非糖尿病大鼠组 (NDIP组 )、非IP糖尿病大鼠组 (DNIP组 )和非IP非糖尿病大鼠组 (NDNIP组 )各 11只。记录II导联心电图。取心脏切片染色 ,计算心肌缺血范围和心肌坏死范围。结果　各组间心肌缺血范围无显著差异 (P >0 .0 5 )。DIP组心肌坏死范围较DNIP组明显减小 (P <0 .0 1)。DNIP组室性心律失常增多 ,尤其心室颤动较其他各组显著增多 (P <0 .0 1)。结论　缺血预适应可以减轻糖尿病大鼠随后较长时间缺血 再灌注对心肌的严重损害 ,能减少心肌坏死范围和降低心室颤动的发生率。     

黄连解毒汤对大鼠急性心肌缺血再灌注损伤的保护作用

目的 观察黄连解毒汤对在体大鼠急性心肌缺血再灌注损伤(I/R)的保护作用,并探讨其作用机制.方法 采用SD大鼠心肌缺血再灌注模型(I/R),将56只SD大鼠随机等分为7组:假手术组、心肌缺血再灌注组、溶剂(%CMC-Na)对照组、黄连解毒汤(HLJDT)低剂量组、HLJDT中剂量组、HLJDT高剂量组,复方丹参组.连续给药7 d,末次给药24 h后,复制大鼠心肌I/R损伤模型.测定血清肌酸激酶(CK)、肿瘤坏死因子(TNF-α)、IL-1β水平,测量心肌梗死范围,取心肌组织检测 NF-κB.结果 与假手术组比较,缺血再灌注组血清TNF-α、IL-1β、CK水平明显增高(P<0.05),梗死范围明显增加(P<0.05),且NF-κB表达明显增高(P<0.05);实验组较缺血再灌注对照组的TNF-α、IL-1β、CK、NF-κB水平明显降低,梗死范围明显降低(P<0.05).结论 黄连解毒汤显著缩小心肌梗死面积,降低心肌酶,减少心肌细胞内TNF-α、IL-1β、CK、NF-κB蛋白的表达,发挥对缺血再灌注心肌的保护作用.     

白藜芦醇对糖尿病大鼠心肌缺血再灌注损伤时炎性反应的影响

目的研究白藜芦醇预处理对糖尿病大鼠心肌缺血再灌注损伤的作用,以及对炎性反应的影响。 方法取糖尿病模型制备成功的SD大鼠30只,采用随机数字表法分为3组（n=10）：假手术组（Sham组）、心肌缺血再灌注组（MI/R组）和心肌缺血再灌注+白藜芦醇组（MI/R+Res组）。B超测量左心室的射血分数（LVEF）以及左室短轴缩短率（FS）,于再灌注末时处死5只大鼠,用TTC染色法测定心肌梗死面积,另再处死5只大鼠,经腹主动脉取血测心肌损伤标志物乳酸脱氢酶（LDH）和肌酸激酶同工酶（CK-MB）的浓度,采用ELISA法检测血清的肿瘤坏死因子-α（TNF-α）,白介素-6（IL-6）,细胞间黏附分子-1（ICAM-1）,并取心肌组织,通过RT-PCR法测TNF-α,IL-6,基质金属蛋白酶-9（MMP-9）的含量。 结果与Sham组比较,MI/R组与MI/R+Res组的LDH和CK-MB浓度,血清TNF-α,IL-6,ICAM-1含量以及心肌梗死面积均显著增高,LVEF和FS显著降低,心肌TNF-α,IL-6,MMP-9的mRNA表达增加（均P<0.05）;与MI/R组比较,MI/R+Res组的LDH和CK-MB浓度,血清TNF-α,IL-6,ICAM-1含量以及心肌梗死面积均显著降低,LVEF和FS显著升高,TNF-α,IL-6,MMP-9的mRNA表达减少（均P<0.05）。 结论白藜芦醇预处理可以减轻糖尿病大鼠心肌缺血再灌注损伤时的炎性反应。     

丹皮酚对心肌缺血再灌注损伤大鼠模型肿瘤坏死因子-α和Toll样受体4表达的影响

目的探讨丹皮酚对大鼠心肌缺血再灌注损伤保护中肿瘤坏死因子(TNF)-α及Toll样受体(TLR)4表达的影响。方法清洁级成年雄性SD大鼠36只随机分为假手术组、缺血再灌注组、丹皮酚低剂量组和丹皮酚高剂量组每组9只;通过结扎左冠脉前降支30 min再灌注2 h建立大鼠心肌缺血再灌注模型。通过TTC染色法检测大鼠梗死心肌体积;ELISA法检测血液中TNF-α的含量;通过免疫组化法检测缺血坏死心肌组织TLR4的表达。结果与缺血再灌注组相比,丹皮酚低剂量组和丹皮酚高剂量组心肌梗死体积减小,TNF-α表达减少;心肌组织TLR4水平明显降低;其中丹皮酚高剂量组更明显。结论丹皮酚能够明显降低大鼠心肌缺血再灌注损伤,这种作用可能与减轻缺血再灌注中大鼠心肌TNF-α及TLR4表达有关。     

芹菜素预处理对缺血再灌注大鼠心肌肿瘤坏死因子-α表达的影响

目的研究芹菜素对缺血再灌注大鼠心肌肿瘤坏死因子-α(TNF-α)表达的影响,探讨抗心肌缺血再灌注损伤的可能机制。方法将Wistar大鼠随机分为5组,假手术组、缺血再灌注对照组、溶剂对照组、芹菜素低剂量组、芹菜素高剂量组。采用结扎左冠脉前降支制作缺血再灌注模型,心肌缺血30 min,再灌注2 h。心肌苏木素碱性品红苦味酸(Hematoxylin basic fuchsin picric,HBPF)染色观察心肌形态学改变,免疫组化染色检测心肌组织TNF-α的表达。结果芹菜素组可降低心肌组织TNF-α的表达,与缺血再灌注对照组比较有统计学意义(P<0.05)。结论芹菜素对缺血再灌注心肌的保护作用可能与减少心肌TNF-α的表达有关。     

β-谷甾醇对大鼠心肌缺血再灌注损伤和ERK1/2信号通路的影响

目的研究β-谷甾醇对大鼠心肌缺血再灌注损伤和ERK1/2信号通路的影响。方法 30只SD雄性大鼠随机分成3组:假手术组、模型组和β-谷甾醇处理组;采用HE染色观察大鼠心肌组织损伤,监测大鼠心脏指数(CI)、每搏量(SV)和每搏指数(SI)等心肌功能指标的变化;采用酶联免疫吸附剂法测定大鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、活性氧(ROS)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、白介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)的含量;采用蛋白印记法检测大鼠心脏组织中细胞外调节蛋白激酶(ERK1/2)、B淋巴细胞瘤-2(Bcl-2)和B淋巴细胞瘤-2结合蛋白X(Bax)的表达。结果与假手术组相比,模型组大鼠心肌指标CI、SV和SI,血清中SOD水平及心脏组织中Bcl-2的表达均显著下降,血清中MDA、ROS、CK、CK-MB、IL-1β、IL-6、TNF-α和心脏组织中ERK1/2和Bax的表达显著上升(P 0. 05);与模型组相比,β-谷甾醇处理组大鼠心肌指标CI、SV和SI,血清中SOD水平和心脏组织中Bcl-2的表达均显著上升,血清中MDA、ROS、CK、CK-MB、IL-1β、IL-6、TNF-α和心脏组织中ERK1/2和Bax的表达显著下降(P 0. 05)。结论β-谷甾醇可保护大鼠心肌缺血再灌注损伤,可能参与ERK1/2信号通路,缓解心肌缺血再灌注大鼠出现的氧化应激和炎症损伤,并抑制其心肌细胞的凋亡。     

原发性高血压患者血清Ⅰ型和Ⅲ型前胶原水平与左心室舒张功能关系的研究

目的研究血清Ⅰ型和Ⅲ型前胶原(procollagen,PC)水平与左心室舒张功能(LVDF)的相关性.方法采用放射免疫分析法,测定72名原发性高血压患者及20名同年龄健康者的血清PC Ⅰ、PCⅢ和肿瘤坏死因子α(TNF-α)的水平,并用超声测量左心室解剖和舒缩功能参数.结果高血压组血清PC Ⅰ、PCⅢ和TNF-α较对照组显著升高(P值分别为P<0.005,P<0.001,P<0.001);高血压伴舒张功能减退者血清PC Ⅰ和PCⅢ水平显著高于高血压但舒张功能正常者(PC ⅠP<0.05;PCⅢP<0.01).血清PC Ⅰ浓度与VA(二尖瓣心房收缩期流速)呈正性直线相关(r=0.268;P<0.05),血清PCⅢ浓度与VE(二尖瓣舒张早期流速)呈负性直线相关(r=-0.271;P<0.05);血清PC Ⅰ和PCⅢ浓度均与VE/VA呈负性直线相关(PC Ⅰ与VE/VAr=-0.226;P<0.05;PCⅢ与VE/VAr=-0.336;P<0.01);血清PCⅢ浓度与TNF-α浓度呈正性直线相关(r=0.338;P<0.01).结论(1)PC Ⅰ和PCⅢ浓度可以作为评价心肌纤维化程度的间接指标,并可能成为临床上诊断高血压患者LVDF减退的生化指标;(2)原发性高血压患者血清TNF-α水平升高,说明TNF-α可能参与了高血压或心肌纤维化的病理生理过程.     

ERK参与缺血后处理的心肌保护作用机制研究

目的 观察缺血后处理对大鼠心肌缺血-再灌注损伤的保护作用,并探讨其可能的机制.方法 选择Wistar大鼠24只,建立大鼠心肌缺血-再灌注损伤模型,随机分为3组:对照组(I/R组)、缺血后处理组(I-postC组 )、抑制剂组(I-postC+ERK抑制剂组).再灌注结束后腹主动脉插管取血测定血清生化指标,剖取左心室计算心肌梗死面积.结果 与I/R组相比,I-postC组心肌梗死面积减少,血清乳酸脱氢酶(LDH)、心肌肌酸激酶同工酶(CK-MB)活性及丙二醛(MDA)含量降低,血清超氧化物歧化酶(SOD)活性增加;抑制剂组与I-postC组相比,心肌梗死面积增大,血清LDH、CK-MB活性及MDA含量升高,血清SOD活性减弱.结论 心肌缺血后处理对实验性大鼠心肌缺血-再灌注损伤有明显的保护作用,该作用可能与细胞外调节蛋白激酶(ERK)信号传导通路有关.     

己酮可可碱对大鼠心肌损伤的保护作用

目的 探讨己酮可可碱(PTX)对心肌损伤的保护作用及机制.方法 建立心肌缺血再灌注(I/R)模型,采用Langendorff灌流装置.120只Wistar大鼠随机分为正常组、缺血组、I/R 5、10、20、30 min组,相应的PTX(100 μmol/L)治疗组,持续观察PTX对血流动力学指标的影响.ELISA法检测心肌组织中的肿瘤坏死因子-α(TNF-α)含量. 结果缺血前及灌注期PTX 100 μmol/L给药能明显恢复大鼠I/R前后心脏的左室发展压(P<0.05),左心室舒张末期压亦明显下降;100 μmol/L PTX治疗组在I/R 5 min时明显降低TNF-α的含量(P<0.05).结论 PTX提高大鼠缺血缺氧后心肌收缩力的恢复水平,增强心肌缺血缺氧的耐受性.改善心肌I/R引起的TNF-α生成可能是其心肌保护作用的机制之一.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.