脑缺血Akt和MAPK磷酸酶负性调节c-Jun N端激酶信号通路

目的：探讨脑缺血再灌后Akt和MAPK磷酸酶与JNK活性下调的关系。方法：采用成年清洁级雄性SD大鼠，建立四动脉阻断前脑缺血再灌注模型。缺血10min后再灌注不同时间（15min，1h，4h，24h）。侧脑室分别给予P13K抑制剂LY294002（LY）和MAPK磷酸酶抑制剂放线菌酮（CHO）。免疫印迹观察P-Akt和P-JNK蛋白水平变化。结果：脑缺血再灌注4h，JNK的活性能被Akt抑制剂LY294002增强，表明激活的Akt能够下调JNK信号通路。而MAPK磷酸酶抑制剂放线茵酮能上调缺血后JNK活性，提示MAPK磷酸酶通过去磷酸化参与了JNK的活性抑制。结论：前脑缺血再灌后，激活Akt和MAPK磷酸酶参与了JNK信号通路负性调节，是抑制JNK诱导缺血后中枢神经损伤的重要机制。

Relationship Between Akt and MAPK Phosphatase and Activity of c-Jun N-terminal Kinase in Rats after Cerebral Ischemia Reperfusion

Objective： To investigate the relationship between the of c-Jun N-terminal kinase （JNK） pathway and Akt and MKP Methods： Rats in the experimental group were subjected to four-vessel occlusion method, endured 10 min ischemia followed by reperfusion for 15min, lh, 4h and 24h to examine phosphorylation of JNK and its upstream Akt in the rat hippocampi. The PI3K inhibitor LY294002 and MAPK phosphatase inhibitor cycloheximide were administrated to the rat hippocampi to observe the change of JNK activity. Results： JNK activity at 4h was enhanced obviously, which suggested that activated Akt suppresses the JNK pathway. Moreover, the JNK activity at 4h was also largely enhanced by cycloheximide, which indicated that the inactivation of JNK by phosphatases occurs at about 4 h via its dephosphorylation. Conclusion： Both Akt and MAPK phosphatase negatively regulate JNK pathway during cerebral ischemia in rat hippocampi.