ERK1/2 MAPKs在大鼠肝移植缺血预处理保护效应中的作用

目的:研究有丝分裂原蛋白活化激酶家族中的细胞外信号调节激酶(external-signal regulated kinases/mitogen activated protein kinase,ERK1/2 MAPKs)信号转导通路在大鼠肝移植供肝缺血预处理保护效应中的作用.方法:大鼠随机分为4组(n=6):假手术对照组(A组)、缺血再灌注肝移植组(B组)、缺血预处理肝移植组(C组)、丝裂原蛋白活化激酶(MEK)抑制剂(PD98059)干预的缺血预处理肝移植组(D组),术后检测各组血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)的活性以及肝组织ERK1/2 MAPKs磷酸化水平,通过透射电镜观察各组细胞形态学改变. 结果:B、D组血清ALT、AST的活性显著高于A组,而C组升高不明显.C组的肝组织ERK1/2 MAPKs磷酸化水平显著升高,B、D组升高不明显.细胞形态学检查结果显示,B、D组供肝细胞破坏严重,C组供肝细胞结构改变较轻微. 结论:缺血预处理对供肝细胞起到保护作用,ERK1/2 MAPKs信号转导通路在保护效应中发挥重要的作用.

Role of ERK1/2 MAPKs signal transduction pathways in protective effects of liver ischemic preconditioning during liver transplantation

Objective:To elucidate the role of ERK1/2 MAPKs signal transduction in the protective effects of ischemic preconditioning during liver transplantation. Methods: Twenty-four rats were equally randomized into 4 groups: sham control (group A); liver transplantation (group B); ischemic preconditioning+liver transplantation (group C), and MEK inhibitor intervention+ischemic preconditioning+liver transplantation (group D). Serum AST and ALT were detected after operation and cellular ultrastructures were observed by transmission electron microscopy. Liver tissue ERK1/2 MAPKs phosphorylation activities were evaluated through determining ERK-1 protein phosphorylation by Western blotting. Results: Serum ALT and AST activity in group B and group D was significantly higher than those in group A, and remained normal in group C. Liver tissue ERK1/2 MAPKs phosphorylation activity increased significantly in group C, and the activation effect was inhibited in group B and D. Cellular ultrastructure was obviously damaged in group B and group D, and the damage was prevented in group C.Conclusion: Ischemic preconditioning has a protective effect on transplanted liver cells in which ERK1/2 MAPKs pathway plays a pivotal role.