永久性大脑中动脉闭塞大鼠纹状体P—SAPK/JNK表达与神经元凋亡的相关性

目的探讨永久性大脑中动脉闭塞（permanent middle cerebral artery occlusion，pMCAO）大鼠纹状体P-SAPK／JNK表达与神经元凋亡的相关性。方法54只Sprague—Dawley雄性大鼠随机分为假手术组以及pMCAO1h、3h、6h、12h和24h组，每组9只。应用TUNEL法检测纹状体凋亡神经元，免疫组织化学染色法检测纹状体P—SAPK／JNK核转位，Western印迹法检测P-SAPK／JNK蛋白表达。结果pMCAO 1h纹状体TUNEL和P—SAPK／JNK阳性细胞数量显著增多（P=0．0001），6h达高峰，12h时TUNEL阳性细胞减少，但仍高于假手术组（P=0．0002）。Western印迹分析显示，pMCAO后纹状体P—SAPK／JNK蛋白表达水平显著增高，且时程变化与免疫组化染色结果一致。纹状体神经元凋亡与P—SAPK／JNK蛋白表达呈显著正相关（r=0．984，P=0．0004）。结论脑缺血可能通过激活P-SAPK／JNK诱导纹状体神经元凋亡。

The correlation between the expression of P-SAPK/JNK and neuronal apoptosis in the striatum during penmnent middle cerebral artery occlusion in rats

Objective To investigate the correlation between the expression of P-SAPK/ JNK and neuronal apoptosis in the striatum during permanent middle cerebral artery occlusion （pMCAO） in rats. Methods Fifty-four male Sprague-Dawley rats were randomly divided into sham operation group and pMCAO 1-, 3-, 6-, 12-, and 24-hour groups （n =9 in each group）. Apoptotie neurons in the striatum during cerebral ischemia were detected by TUNEL assay, the nuclear translocation of P-SAPK/JNK in the striatum by immunohistochemical staining, expressions of P-SAPK/JNK protein by Western blot. Results The numbers TUNEL- and P-SAPK/ JNK-positive cells in the striatum at 1 hour after pMCAO increased sigfificantly （P =0. 000 1） , and reached the peak at 6 hours. The numbers of TUNEL-positive cells decreased at 12 hours, however, it still higher than the sham operation group （P = 0. 000 2）. Western blot analysis showed that the expression of P-SAPK/JNK after pMCAO increased significantly, and the time-course change was in accord with the result of immunohistochemical staining. Neuronal apoptosis in the striatum was significantly positively correlated with the expression of P-SAPK/ JNK （r =0. 984, P =0. 000 4）. Conclusions Cerebral ischemia may induce neuronal apoptosis in the striatum through the activation of P-SAPK/JNK.