糖蛋白Ⅱb/Ⅲa受体抑制剂对脓毒症大鼠急性肺损伤的保护作用

Protective effects of Glycoprotein Ⅱb/Ⅲa receptor inhibitors against the sepsis-induced acute lung injury of rat

目的 采用盲肠结扎穿孔术复制大鼠脓毒症模型,研究糖蛋白（glycoprotein,GP）Ⅱb/Ⅲa受体抑制剂依替巴肽（Eptifibatide）对脓毒症大鼠急性肺损伤的保护作用.方法 64只雄性SD大鼠随机分为三组：假手术组16只、盲肠结扎穿孔（cecal ligation and puncture,CLP）组和治疗组各24只,每组再均分为6 h、10 h、14 h和18 h四个亚组（假手术组每个亚组均4只,CLP组和治疗组各亚组均6只）,其中治疗组术后4 h、8 h、12 h和16 h经大鼠尾静脉给予依替巴肽（7.5 mg/kg）干预.术后间隔不同的时间后将大鼠放血活杀,取出待测肺组织,检测肺微血管通透性改变、肺湿/干质量（W/D）比值,进行肺组织形态学观察和病理评分,并检测肺微血管内皮细胞的凋亡情况.结果 CLP组大鼠肺组织6 h开始出现损伤,10 h、14 h和18 h损伤逐渐加重,损伤在CLP后18 h最重;与CLP组比较,治疗组各时间点大鼠肺微血管通透性明显降低（P〈0.05）,致使肺组织W/D值亦明显降低（P〈0.05）,肺组织炎细胞浸润、水肿、出血等损伤表现减轻,肺组织病理评分明显降低（P〈0.05）;治疗组术后各观察时间点肺微血管内皮细胞的凋亡率明显降低,与CLP组比较差异均有统计学意义（P〈0.05）.结论 GP Ⅱb/Ⅲa受体抑制剂依替巴肽对脓毒症大鼠急性肺损伤有保护作用.

Objective To investigate the effects of Glycoprotein Ⅱ b/Ⅲ a receptor inhibitors eptifibatide against acute lung injury in rat septic models. Methods 64 SD male rats were randomly divided into three groups： sham operation, cecal ligation and puncture （CLP） and treatment group. Each group was divided into four sub -groups： 6 h, 10 h, 14 h and 18 h after operation （four rats in each sham sub - groups, six rats in each CLP and treatment sub - groups）. In treatment group, rats were treated with eptifibatide （7. 5 mg/kg） at g h, 8 h, 12 h and 16 h. The permeability of microvasculature, water contents, pathological tissue scores and the apoptosis of microvascular endothelial cells in lung microvasculature were examined at 6 h, 10 h, 14 h and 18h after operation. Results The rat lung injury happened as early as 6 h of CLP operation ; and became worse as time went on（10 h,lg h and 18 h） ; the damage was most serious in 18 h of CLP operation. Compared with CLP group, pulmonary microvascular protein leak, as assessed by Evans blue dye, was significantly reduced in treatment groups （ P 〈 0.05 ） ; and the pulmonary wet/dry weight ratio was lower （ P 〈 0.05 ）, the pathological tissue scores was markedly decreased （ P 〈 0.05 ） in treatment group ; the apoptosis of lung microvascular endothelial cells in treatment group at 6 h, 10 h, 14 h and 18 h were significantly decreased compared with the CLP group （ P 〈 0.05 ）. Conclusion Glycoprotein H b/Ill a receptor inhibitors eptifibatide could protect rat from acute lung injury induced by sepsis. [Key words] Sepsis; Acute lung injury（ALI） ; Eptifibatide; GPⅡb/Ⅲa; Apoptosis decreased compared with the CLP group （ P 〈 0.05 ）. Conclusion Glycoprotein Ⅱb/Ⅲa receptor inhibitors eptifibatide could protect rat from acute lung injury induced by sepsis.