丝裂原激活蛋白激酶信号通路在肝脏缺血预处理细胞保护效应中的作用  

Protecting effects of p44/42 MAPK signal transduction pathway on hepatocytes in ischemic preconditioning

作　　者：高毅[1] 王瑜[1] 潘明新[1] 孙尔维[1] 单毓强[1] 

机构地区：[1]第一军医大学附属珠江医院器官移植科,广州510280

出　　处：《中华肝脏病杂志》2003年第3期166-169,共4页Chinese Journal of Hepatology

基　　金：广东省自然科学基金(No.001086)

摘　　要：目的 研究p44/42丝裂原激活蛋白激酶(MAPK)信号通路在肝脏缺血预处理细胞保护效应中的作用。方法 建立体内和体外肝脏缺血预处理模型,应用蛋白激酶C(PKC)抑制剂和MAPK抑制剂,通过检测p44/42MAPK磷酸化水平,细胞活力,血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的活性变化,同时观察光镜细胞形态学损害,对相关数据进行统计学处理。 结果 体内和体外的缺血预处理两部分实验都观察到相似的结果。和缺血再灌注组比较,预处理组的p44/42 MAPK磷酸化水平显著增高,肝细胞结构损伤改变较小,血清ALT、AST水平显著降低,缺血再灌注组的ALT、AST水平分别为(762.8±130.5)U/L和(820.9±111.3)U/L,预处理组的ALT、AST水平分别为(281.0±35.6)U/L和(407.7±73.7)U/L;和缺血预处理组相比,PKC抑制剂组和丝裂原蛋白激酶(MEK)抑制剂组相应的观察指标呈相反的变化,p44/42 MAPK磷酸化激活显著减少,肝组织细胞结构出现较明显的损伤改变,血清ALT、AST水平显著升高,PKC抑制剂组和MEK抑制剂组的ALT、AST水平分别为(645.61±90.4)U/L、(678.6±136.5)U/L和(466.2±82.8)U/L、(732.9±91.1)U/L。 结论 肝脏缺血预处理细胞保护作用中,p44/42 MAPK通路起到至关重要的作用。Objective To investigate the significance of PKC and p44/42 mitogen-activated protein kinase (MAPK) signal transduction in ischemic preconditioning (IP). Methods Through liver cell IP models, PKC inhibitor and MEK inhibitor were utilized to analyze the phosphorylation level of p44/42 MAPK and cell viability was also observed. Rat liver IP models were established which were treated with various drugs. Then the phosphorylation level of p44/42 MAPK in vivo and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) concentrations were detected. And cellular structures were observed under light microscopy. Results Similar results were obtained in vivo and in vitro IP models. Compared with the ischemia reperfusion (IR) group in vivo, the phosphorylation level of p44/42 MAPK was obviously increased in IP treated rats (q = 27.217, P < 0.01), and the cellular structure injured slightly. The concentrations of serum ALT and AST in IP group were significantly lower than those in IR group (281.0 U/L±35.6 U/L vs 762.8 U/L±130.5 U/L and 407.7 U/L±73.7 U/L vs 820.9 U/L±111.3 U/L, P < 0.01). However, opposite changes were found in PKC and MEK inhibited groups, when compared to IP group. The phosphorylation level of p44/42 MAPK was obviously decreased, the liver tissues injured evidently, and the concentrations of serum ALT and AST (645.61 U/L± 90.4 U/L, 678.6 U/L±136.5U/L and 466.2 U/L±82.8 U/L, 732.9 U/L± 91.1 U/L, respectively) were significantly greater than those in IP group. Conclusion These results suggest that p44/42 MAPK pathway plays a vital role in the protection of hepatocytes in ischemic preconditioning.

关 键 词：丝裂原激活蛋白激酶 信号通路 肝脏缺血 缺血预处理 大鼠 信号转递 L02肝细胞株 

分 类 号：R657.3[医药卫生—外科学]