血小板拮抗剂氯吡格雷对脓毒症大鼠的保护作用

发布时间：2018-03-31 04:31

本文选题：脓毒症　切入点：血小板　出处：《中南大学》2014年硕士论文

【摘要】：目的：脓毒症常常伴随不同程度的凝血功能异常,血小板在炎症和凝血反应过程中均发挥着重要作用。以往研究显示,在大鼠内毒素血症模型中,氯吡格雷可以改善肝肺组织的病理改变,减轻促炎介质IL-6和TNF-α及肝肺组织中HMGB1的水平。本研究以SD大鼠作为研究对象,经盲肠结扎穿刺(CLP)复制脓毒症模型,探讨血小板拮抗剂氯吡格雷对脓毒症大鼠生存率、血小板-白细胞相互作用和白细胞组织因子表达及内皮细胞激活的影响。方法：将雄性SD大鼠随机分为四组：1.假手术组；2.假手术+氯吡格雷组；3.CLP组；4.CLP+氯吡格雷组。观察术后7天内各组大鼠的生存率；并采用流式细胞术检测各组大鼠血小板和白细胞激活,血小板-白细胞相互作用及白细胞表面组织因子的表达；采用Elisa试剂盒分别检测大鼠ICAM-1, E-Selectin, PSGL-1的血浆水平。结果： (1)生存率：CLP组大鼠生存率与假手术组/假手术+氯吡格雷组相比显著下降(p0.05)；而CLP+氯吡格雷组大鼠生存率与CLP组相比显著升高(p0.05)。(2)流式细胞术检测：术后24小时,与假手术组/假手术+氯吡格雷组相比,CLP组大鼠血小板、白细胞激活,血小板-白细胞相互作用及白细胞组织因子表达明显增高(p0.05)；而与CLP组相比,CLP+氯吡格雷组大鼠血小板和白细胞激活,血小板-白细胞相互作用及白细胞组织因子表达显著降低(p0.05)。(3)Elisa检测：术后12小时,CLP组大鼠血浆中ICAM-1, E-Selectin的水平与假手术组/假手术+氯吡格雷组相比显著升高(p＜0.05); CLP+氯吡格雷组大鼠血浆中ICAM-1, E-Selectin的水平均显著低于CLP组(p0.05)；但各组大鼠血浆PSGL-1水平没有明显差别(p0.05)。术后24小时,CLP组大鼠血浆中ICAM-1、PSGL-1的水平与假手术组／假手术+氯吡格雷组相比显著升高(p＜0.05); CLP+氯吡格雷组大鼠血浆中ICAM-1、PSGL-1水平显著低于CLP组(p0.05),而各组大鼠血浆E-Selectin水平没有明显差别(p0.05)。结论：血小板拮抗剂氯吡格雷显著抑制脓毒症所致的血小板、白细胞和内皮细胞的激活及血小板-白细胞粘附和白细胞组织因子表达的上调,并提高脓毒症大鼠的生存率。
[Abstract]:Objective:. Sepsis is often accompanied by varying degrees of coagulation dysfunction, and platelets play an important role in inflammation and coagulation. Previous studies have shown that in the rat model of endotoxemia, Clopidogrel could improve the pathological changes of liver and lung tissues and reduce the levels of proinflammatory mediators IL-6 and TNF- 伪 as well as the levels of HMGB1 in liver and lung tissues. In this study, SD rats were used to establish septic model by cecal ligation and puncture. To investigate the effects of clopidogrel, a platelet antagonist, on survival rate, platelet-leukocyte interaction, leukocyte tissue factor expression and endothelial cell activation in septic rats. Methods:. Male Sprague-Dawley rats were randomly divided into four groups: 1. Sham-operated clopidogrel group 3.CLP group 3.CLP clopidogrel group 4.The survival rate of each group was observed 7 days after operation, and platelet and leukocyte activation were detected by flow cytometry. The plasma levels of ICAM-1, E-Selectin and PSGL-1 were detected by Elisa kit. Results:. 1) the survival rate of rats in the CLP clopidogrel group was significantly higher than that in the CLP group, and the survival rate of the rats in the CLP clopidogrel group was significantly higher than that in the CLP group. Flow cytometry was used to detect: 24 hours after operation, the survival rate of the rats in the clopidogrel group was significantly higher than that in the CLP group. Compared with sham operation group / clopidogrel group, platelet and leukocyte activation were observed in CLP group. Platelet-leukocyte interaction and leukocyte tissue factor expression were significantly increased in CLP group, and platelet and leukocyte activation in clopidogrel group was higher than that in clopidogrel group. Platelet-leukocyte interaction and leukocyte tissue factor expression decreased significantly (P < 0.05). CLP chloride level in plasma of rats in 12 hours after operation was significantly higher than that in sham operation group and clopidogrel group (P < 0.05), and the level of ICAM-1 and E-Selectin in plasma was significantly higher than that in sham operation group / clopidogrel group (P < 0.05). The plasma levels of ICAM-1 and E-Selectin in the piogrel group were significantly lower than those in the CLP group, but there was no significant difference in the plasma PSGL-1 level between the two groups. 24 hours after operation, the plasma ICAM-1 and PSGL-1 levels in the control group and the sham operation / clopidogrel group were higher than those in the sham operation group and clopidogrel group. The plasma levels of ICAM-1 and PSGL-1 in the CLP clopidogrel group were significantly lower than those in the CLP group (P < 0.05), but there was no significant difference in the plasma E-Selectin level between the two groups. Conclusion:. Clopidogrel, a platelet antagonist, significantly inhibited the activation of platelets, leukocytes and endothelial cells induced by sepsis, as well as the up-regulation of platelet-leukocyte adhesion and leukocyte tissue factor expression, and increased the survival rate of septic rats.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R459.7

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