摘要
目的 研究蛋白激酶C(PKC)、P44 / 42丝裂原激活蛋白激酶 (P44 / 42mitogen activatedproteinkinase ,P44 / 42MAPKs)、热休克蛋白 70 (HSP70 )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的蛋白激酶激酶 (mitogen activatedproteinkinasekinase ,MEK)抑制剂 ,通过检测PKC和P44 / 42MAPKs磷酸化水平、HSP70表达量、血清天氡氨酸转氨酶、丙氨酸转氨酶的活性变化 ,同时观察光镜和电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 <0 0 1) ,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 <0 0 1) ;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。
Objective To investigate the significance of PKC,P44/42 MAPKs and HSP70 signal transduction in IP. Methods Through an in vivo rat liver IP model ,PKC inhibitor, activator and MEK inhibitor were utilized to analyze the phosphorylation of PKC and P44/42 MAPKs. HSP expression ,AST/ALT concentration, cellular structure and ultrastructure were also observed. All the data were statistically analyzed. Results Compared with the control 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 the expression of HSP were also obviously increased. In contrast, opposite changes were found in PKC or MEK inhibited groups, the phosphorylation PKC was decreased in PKC inhibited group (P<0.01). Conclusion The 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.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2003年第3期242-246,共5页
National Medical Journal of China
基金
广东省自然科学资助项目 ( 0 0 10 86 )
