肝脏缺血预处理所致PKC活性改变及细胞内信号转导机制的实验研究

目的：研究大鼠肝脏缺血预处理保护效应中蛋白激酶C(PKC)的活性改变及细胞内信号可能的转导机制。方法：通过建立大鼠肝脏缺血预处理模型,应用ＰＫＣ抑制剂、激动剂,检测PKC和P44/42MAPKs磷酸化水平的变化,同时观察光镜下细胞形态学损害。结果：与缺血再灌注（IR）组比较,预处理（IP）组和PKC激动剂组的PKC磷酸化水平显著提高(P<0 01), 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IP组相比,PKC抑制剂组相应指标呈相反变化,PKC磷酸化水平显著降低(P<0 01)，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的激活对P44/42MAPKs通路激活起重要作用,PKC对P44/42MAPKs起正性调控作用,HSP70表达受P44/42MAPKs的调控。

Study on the PKC in signal transduction pathway in hepatocyte ischemic preconditioning

Objective To investigate the mechanism of alternation of PKC activify in liver ischemia preconditioning(IP). Methods After establishment of rat liver IP model, PKC inhibitor and activator were utilized to analyze the phosphorylation of PKC and P44/42MAPKs and HSP expression, and cellular structure was also observed. All of the data were statistically analyzed. Results Compared with the control group without IP, the phosphorylation of PKC was significantly increased in IP treated models and PKC activated group(P< 0.01), and P44/42 MAPKs and expression of HSP 70 were also obviously increased, but with little change of hepatic cellular structure. In contrast, opposite changes were found in PKC inhibited groups, the phosphorylation PKC was decreased in PKC inhibited group(P< 0.01) and marked changes in hepatic cellular structure. Conclusions The IP model has shown that PKC activation plays a pivotal role in the activation of P44/42 MAPKs pathway that participates in the preservation of liver cells. At the same time, HSP expression is regulated by signals in P44/42 MAPKs pathway.