c-Jun氨基末端激酶在高血糖加重脑缺血性损伤中的作用

The effect of c-Jun NH_2-terminal kinase on hyperglycemia-exaggerated cerebral ischemia damage

目的探讨c-Jun氨基末端激酶(JNK)在高血糖加重大鼠脑缺血再灌注损伤中的作用。方法建立大鼠全脑缺血模型,通过免疫组织化学、Western blot,研究正常血糖和高血糖大鼠脑缺血时JNK的表达。结果正常血糖缺血组和高血糖缺血组大脑皮质和海马CA1区随着缺血再灌注时间的延长,JNK表达明显升高,与对照组比较有统计学意义(P<0.01),但两组在缺血再灌注相同时间点比较JNK表达均无统计学意义(P>0.05)。Western blot分析可见,正常血糖组再灌注后1h,JNK达到高峰;高血糖组再灌注后3h,JNK达到高峰,与对照组比较有统计学意义(P<0.05),高血糖组与正常血糖组在各缺血再灌注时间点比较无统计学意义(P>0.05)。结论高血糖可加重脑缺血再灌注损伤;JNK参与了脑缺血性损伤的发生,但高血糖并不能明显增加脑缺血性损伤时JNK的表达,故在高血糖加重脑缺血性损伤中JNK可能不发挥主要作用。

Objective To determine whether activation of JNK plays a role in the hyperglycemia-mediated ischemic damage.Methods Fifty male Sprague-Dawley（SD） rats,weighing 250-300g,cerebral ischemia of 0.5h duration was induced by bilateral clamping of the carotid arterial plus hypotension by withdrawing blood.The groups were randomly divided into three groups.Normoglycemic operation groups,hyperglycemic operation groups and sham operation groups.Immunohistochemistry and Western blotting techniques were used to detect the expression of JNK and the relationship between JNK and cerebral ischemia damage.Results showed that levels of JNK increased in both normo-and hyperglycemic brains following blood reperfusion compared with sham operation groups in the neocortex and hippocampal CA1（P0.01）.The level of JNK increased in both normo-and hyperglycemic brain following blood reperfusion for 1hrs and persisted up to 3hrs.The numbers of positive neurones in hyperglycemic ischemia was not further enhanced as compared to normoglycemic ischemia of 0.5h duration and followed by 3 and 6 hours of recovery（P0.05）.Compared with sham operation groups,normo-and hyperglycemic cerebral ischemia and ischemia-reperfusion damage significantly increased the expressions of JNK in cortex and hippocampal CA1（P0.05）,but there was no significant difference in the activation of JNK between normoglycemic group and hyperglycemic group by Western blot（P0.05）.Conclusion The hyperglycemia can aggravate cerebral ischemia and ischemia-reperfusion damage,but hyperglycemia dose not increase the expression of JNK,JNK may not contribute to the detrimental effects in the course of neuronal damage.