丝裂原蛋白激酶信号转导通路在机械通气相关性肺损伤中的作用  

The roles of mitogen-activated protein kinase pathway in ventilation-induced lung injury in rats

作　　者：王月兰[1] 姚尚龙[1] 

机构地区：[1]华中科技大同济医学院协和医院麻醉科

出　　处：《中华实验外科杂志》2006年第3期331-333,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(30471661)教育部博士点基金课题资助项目(20020487063)

摘　　要：目的观察机械通气介导肺损伤(VILI)过程中丝裂原蛋白激酶(MAPK)的活性变化以及对细胞因子的影响,从中探讨VILI发生机制和MAPK的作用。方法 72只SD大鼠随机分为未处理的对照组(不行机械通气)、正常通气组、过度通气组和采用MAPK抑制剂SP600125 (JNK)、SB203580(p38)、PD98059(ERK)分别预处理上述3组。机械通气4 h后取大鼠肺组织采用 Western blot方法测定各组的总JNK、ERK、p-38蛋白激酶的表达及其磷酸化水平变化。同时以酶联免疫吸附试验(ELISA)方法测定大鼠肺组织、支气管肺泡灌洗液(BALF)和血浆中的肿瘤坏死因子-α(TNF-α)、巨噬细胞炎性蛋白-2(MIP-2)浓度。结果正常和过度机械通气4 h后均能激活 JNK、ERK、p38激酶,但以过度通气组为著(P<0．01)。过度通气组大鼠肺组织、BALF、血浆中的 TNF-α、MIP-2含量显著高于其他组(P<0．01)。JNK、ERK、p38抑制荆显著降低肺组织、BALF中的TNF-α、MIP-2含量(P<0．05或0．01),且JNK和ERK抑制剂作用强于p38抑制剂。结论过度机械通气激活了肺细胞中的JNK、ERK、p38激酶,且JNK、ERK、p38参与了VILI细胞因子的产生,即MAPK信号转导通路的激活可能是VILI发生机制之一。Objective To evaluate the effects of the mitogen-activated protein kinase pathway （MAPK） on ventihtion-induced lung injury in vivo in rats. Methods Anesthetized male SD rats were randomized into control group, normal ventilation group and overventilation group. Each group had 6 animals. The rats were pretreated with the inhibitors of MAPK in each group. After 4 h ventilation, the activation and the protein expression of MAPK were analyzed by Western blot assay. Cytokine concentrations of TNF-α and MIP-2 in the lung homogenate, bronchoalveolar lavage fluid （BALF） and plasma were detected by ELISA. Results In adult rats, the normal ventilation and the overventilation could elevate the levels of phosphorylation of ERK-1/2, JNK and p38, as well as the concentrations of TNF-α and MIP-2 increased significandy in the lung homogenate, BALF and plasma as compared with the control group （ P 〈 0.01）, but the overventilation did more （ P 〈 0.01）. The MAPK inhibitors, SP600125, SB203580 and PD98059, prevented ventilation-induced activation of JNK, ERK-1/2 and p38, furthermore had a significant effect on ventilation-induced cytokine reiease, which reduced the concentrations of TNF-α and MIP-2 remarkably （P 〈 0.05 or 0.01）. Conclusion Mechanical ventilation triggers specific signalling pathways, such as the MAPK pathways, which may contribute to pulmonary inflammation and cytokine release.

关 键 词：丝裂原蛋白激酶 机械通气 肺损伤 细胞因子 

分 类 号：R563[医药卫生—呼吸系统]