UCF-101对大鼠局灶性脑缺血再灌注后JNK和ERK活性的影响

目的:探讨UCF-101对局灶性脑缺血再灌注大鼠脑内c-Jun氨基末端激酶(JNK)和胞外信号调节酶(ERK)活性的影响,进一步探讨UCF-101对局灶性脑缺血再灌注损伤脑保护作用的机制。方法:采用大脑中动脉线栓法(MCAO)建立大鼠局灶性脑缺血再灌注模型,随机分为假手术组,缺血再灌注组,UCF组,应用TTC检测大鼠脑梗死体积,TUNEL法检测神经元凋亡,Western blot检测ERK和JNK的活性。结果:UCF-101可下调脑缺血再灌注大鼠脑组织JNK蛋白的活性,上调ERK蛋白的活性,并降低梗死体积、坏死和凋亡细胞数。结论:UCF-101对大鼠局灶性脑缺血再灌注损伤有保护作用,抑制JNK凋亡通路、促进ERK生存通路,从而减轻细胞凋亡是其脑保护机制之一。

The Effect of UCF-101 on the Activation of JNK and ERK after Focal Cerebral Ischemia-reperfusion Injury in Rats

Objective:To investigate the neuroprotective effect of 5- 5- (2-nitrophenyl)furfuryliodine]-1,3-diphenyl-2- thiobarbituric acid (UCF-101) on activation of C-Jun NH2-terminal kinases (JNK) and extracelluar-regulated protein kinases (ERK) after cerebral ischemia-reperfusion injury in rats.Methods:The focal cerebral ischemia models of Wistar rats were established by the right middle cerebral artery occlusion (MCAO) with thread occlusion methods. Reperfusion began 1h after the right middle cerebral artery occlusion. Rats were randomly divided into sham operated group, ischemia-reperfusion group and UCF-101 treated group. Brain infarct volume was assessed by 2, 3, 5-triphenyl tetrazolium chloride and TUNEL staining was utilized to evaluate the amount of apoptosis. In addition, expressions of protein JNK and ERK were examined by Western blot analysis.Results:UCF-101 treatment significantly decreased cerebral infarct size and TUNEL-positive cells in hippocampus neurons. Furthermore, UCF-101 treatment decreased JNK and increased ERK expression.Conclusion:UCF-101 treatment has neuroprotective effects against cerebral ischemia-reperfusion injury in rats, and that this may be associated with differentialy regulation of ERK and JNK expression.