活化蛋白C对体外循环大鼠肺的保护作用-东南大学学报医学版

活化蛋白C对体外循环大鼠肺的保护作用

单位：东南大学附属中大医院心胸外科, 江苏南京 210009

分类号：R654.1

出版年·卷·期（页码）：2014·33·第六期（756-760）

摘要：

目的: 探讨活化蛋白C(APC)对体外循环(CPB)所致肺损伤的保护作用.方法: 48只SD大鼠建立CPB模型,随机分为对照组、凝血酶组、APC组、APC+凝血酶组4组,每组12只.CPB开始时分别给药: APC组予APC 0.1 mg·kg^-1,凝血酶组予凝血酶 0.5 U·kg^-1,APC+凝血酶组予APC 0.1 mg·kg^-1+凝血酶 0.5 U·kg^-1,对照组予等量生理盐水.检测各组CPB术前、术后即刻及术后60 min CD11b/CD18、血浆IL-8、中性粒细胞弹性蛋白酶(NE).术后取肺组织称重计算肺湿干重比(W/D).行支气管肺泡灌洗,取灌洗液行白细胞计数、蛋白含量检测,并计算肺毛细血管通透性指数(PMPI);检测肺组织肿瘤坏死因子α(TNF-α)含量.取少许肺组织行光镜病理学检查.结果: 术后肺组织TNF-α含量、肺泡灌洗液白细胞计数、PMPI、W/D、CD11b/CD18、IL-8、NE含量APC组和APC+凝血酶组明显低于对照组和凝血酶组(P<0.05).而凝血酶组各指标均明显高于对照组(P<0.05).结论: 大鼠CPB转流前给予APC 0.1 mg·kg^-1可有效减轻CPB所致全身炎症反应造成的肺损伤,其可能的机制是APC在一定程度上逆转激活的凝血酶对肺的损伤.

Objective: To explore the protective effects of activated protein C(APC)on cardiopulmonary bypass induced lung injury. Methods: Forty-eight SD rats were randomly divided into 4 groups(12 for each group), including control group, thrombin group, APC group and APC+thrombin group, and received respectively APC 0.1 mg·kg^-1 (APC group), thrombin 0.5 U·kg^-1(thrombin group), APC 0.1 mg·kg^-1+thrombin 0.5 U·kg^-1 (APC+thrombin group);control group was given same volume of normal saline. The blood was collected for detecting CD11b/CD18, IL-8, neutrophil elastase(NE) at initiation of cardio-pulmonary bypass(CPB), immediately after the operation, and 60 minutes after the operation. At the end of the experiment, lung tissue was taken for W/D lung weight ratio measurement. Right lung was lavaged and bronchoavleolar lavage fluid(BALF) was collected to count the number of total neutrophil, test protein content and evaluate the pulmonary microvascular permeability index(PMPI). Tissue tumor necrosis factor α (TNF-α) concentration were detected. The lung section pathological examination in each group was performed. Results: Compared with the control group and thrombin group,TNF-α, total neutrophil of BALF,PMPI,W/D, CD11b/CD18, IL-8, NE were significantly lower than those in APC group and APC+thrombin group(P<0.05). Indicators of thrombin group were significantly higher than those in control group (P<0.05). Conclusion: Application of APC (0.1 mg·kg^-1) before cardiopulmonary bypass could attenuate acute lung injury induced by cardiopulmonary bypass, at least in part through that APC reverse the evaluating of the pulmonary microvascular permeability induced by thrombin.

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