南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (08): 1188-.

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蛋白激酶C和丝裂原活化的蛋白酶家族对缺血预处理肝脏的保护作用及其机制

潘明新； 张翌； 李爱辉； 高毅；   

  1. 南方医科大学珠江医院普通外科； 南方医科大学珠江医院普通外科 广东广州510282； 广东广州510282；
  • 出版日期:2006-08-20 发布日期:2006-08-20
  • 基金资助:
    广东省自然科学基金(001086)~~

Protective effect of protein kinase C and mitogen-activated protein kinases and its mechanism in liver ischemic preconditioning

PAN Ming-xin, ZHANG Yi, LI Ai-hui, GAO Yi Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China   

  1. 南方医科大学珠江医院普通外科； 南方医科大学珠江医院普通外科 广东广州510282； 广东广州510282；
  • Online:2006-08-20 Published:2006-08-20

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摘要： 目的研究在肝脏缺血预处理保护效应中蛋白激酶C(PKC)活性改变及细胞内信号转导机制。方法建立大鼠肝脏缺血预处理模型,应用PKC抑制剂、激动剂和丝裂原激活蛋白激酶(MAPK)抑制剂,通过检测PKC和P44/42MAPKs磷酸化水平、HSP70表达量等的变化,同时观察光镜下细胞形态学损害。对相关数据进行统计学处理。结果与缺血再灌注组比较,预处理组和PKC激动剂组的PKC磷酸化水平显著增高(P<001),P44/42MAPKs磷酸化水平、HSP70表达量明显增加,肝细胞结构改变较小。与缺血预处理组相比,PKC抑制剂组相应的观察指标呈相反变化,PKC磷酸化水平显著降低(P<001);MEK抑制剂组的P44/42MAPKs磷酸化激活显著减少,HSP70表达量降低,肝组织细胞结构出现较明显的改变。结论体内缺血预处理保护作用中,PKC激活对P44/42MAPKs通路激活起到至关重要的作用,PKC对P44/42MAPKs起正性调控作用,HSP70表达受P44/42MAPKs调控。 

Abstract: Objective To investigate the protective effects of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs) their and mechanisms in liver ischemic preconditioning. Methods In rat models of liver ischemia-reperfusion (IR) and ischemic preconditioning (IP), the liver function was evaluated by examining serum alanine aminotransferase and aspartate aminotransferase levels, and the morphological changes of the liver cells were observed under microscope. PKC activator phorbol 12-myristate 13-acetate(PMA) and inhibitor chelerythrine(CHE), as well as MEK inhibitor PD98059, were utilized to analyze the phosphorylation of PKC and P44/42 MAPKs. Results Compared with the control rats, the liver function was best protected in rats of IP group, but not in those of IP group with PD98059 or CHE treatment. The rats in IR group showed improved liver function after PMA treatment. Similarly, the phorsphorylation of PKC and P44/42 MAPKs was correlated with the liver function, and highly enhanced PKC and P44/42 MAPKs activity was observed in IP and IR+PMA groups, but decreased activity in IR and IP+CHE groups. Conclusion Phosphorylation of PKC and MAPKs plays a pivotal role in the preservation of the hepatocytes during IP. 

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