本文選題：膿毒癥　切入點(diǎn)：血小板　出處：《中南大學(xué)》2014年碩士論文

【摘要】：目的： 膿毒癥常常伴隨不同程度的凝血功能異常,血小板在炎癥和凝血反應(yīng)過程中均發(fā)揮著重要作用。以往研究顯示,在大鼠內(nèi)毒素血癥模型中,氯吡格雷可以改善肝肺組織的病理改變,減輕促炎介質(zhì)IL-6和TNF-α及肝肺組織中HMGB1的水平。本研究以SD大鼠作為研究對(duì)象,經(jīng)盲腸結(jié)扎穿刺(CLP)復(fù)制膿毒癥模型,探討血小板拮抗劑氯吡格雷對(duì)膿毒癥大鼠生存率、血小板-白細(xì)胞相互作用和白細(xì)胞組織因子表達(dá)及內(nèi)皮細(xì)胞激活的影響。 方法： 將雄性SD大鼠隨機(jī)分為四組：1.假手術(shù)組；2.假手術(shù)+氯吡格雷組；3.CLP組；4.CLP+氯吡格雷組。觀察術(shù)后7天內(nèi)各組大鼠的生存率；并采用流式細(xì)胞術(shù)檢測(cè)各組大鼠血小板和白細(xì)胞激活,血小板-白細(xì)胞相互作用及白細(xì)胞表面組織因子的表達(dá)；采用Elisa試劑盒分別檢測(cè)大鼠ICAM-1, E-Selectin, PSGL-1的血漿水平。 結(jié)果： (1)生存率：CLP組大鼠生存率與假手術(shù)組/假手術(shù)+氯吡格雷組相比顯著下降(p0.05)；而CLP+氯吡格雷組大鼠生存率與CLP組相比顯著升高(p0.05)。(2)流式細(xì)胞術(shù)檢測(cè)：術(shù)后24小時(shí),與假手術(shù)組/假手術(shù)+氯吡格雷組相比,CLP組大鼠血小板、白細(xì)胞激活,血小板-白細(xì)胞相互作用及白細(xì)胞組織因子表達(dá)明顯增高(p0.05)；而與CLP組相比,CLP+氯吡格雷組大鼠血小板和白細(xì)胞激活,血小板-白細(xì)胞相互作用及白細(xì)胞組織因子表達(dá)顯著降低(p0.05)。(3)Elisa檢測(cè)：術(shù)后12小時(shí),CLP組大鼠血漿中ICAM-1, E-Selectin的水平與假手術(shù)組/假手術(shù)+氯吡格雷組相比顯著升高(p＜0.05); CLP+氯吡格雷組大鼠血漿中ICAM-1, E-Selectin的水平均顯著低于CLP組(p0.05)；但各組大鼠血漿PSGL-1水平?jīng)]有明顯差別(p0.05)。術(shù)后24小時(shí),CLP組大鼠血漿中ICAM-1、PSGL-1的水平與假手術(shù)組／假手術(shù)+氯吡格雷組相比顯著升高(p＜0.05); CLP+氯吡格雷組大鼠血漿中ICAM-1、PSGL-1水平顯著低于CLP組(p0.05),而各組大鼠血漿E-Selectin水平?jīng)]有明顯差別(p0.05)。 結(jié)論： 血小板拮抗劑氯吡格雷顯著抑制膿毒癥所致的血小板、白細(xì)胞和內(nèi)皮細(xì)胞的激活及血小板-白細(xì)胞粘附和白細(xì)胞組織因子表達(dá)的上調(diào),并提高膿毒癥大鼠的生存率。
[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- 偽 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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R459.7

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本文編號(hào)：1689182