UCF-101对大鼠脑缺血再灌注后凋亡抑制蛋白XIAP表达的影响

The Effect of UCF-101 on the expression of apoptosis inhibitor protein XIAP during focal cerebral ischemia-reperfusion in rats

目的观察UCF-101对大鼠脑缺血再灌注损伤后神经元凋亡及凋亡抑制蛋白XIAP表达的影响,探讨UCF-101对缺血性脑损伤的神经保护作用。方法采用线栓法建立Wistar大鼠大脑中动脉闭塞(MCAO)2h再灌注模型,随机将大鼠分为假手术组、缺血再灌注组及UCF-101处理组,于再灌注后24h取脑,采用TTC法测梗死体积,TUNEL法检测神经元凋亡,免疫组化法观察脑组织神经元XIAP蛋白的表达。结果假手术组未见梗死现象,偶见凋亡神经细胞,神经元中可见棕黄色XIAP颗粒散在分布于核膜周围胞浆中。与假手术组比较,缺血再灌注组可见梗死灶,脑组织凋亡细胞数明显增加,XIAP的表达明显降低(P<0.05);与缺血再灌注组比较,UCF-101处理组梗死体积明显缩小(P<0.05),脑组织凋亡细胞数减少,XIAP的表达均明显增加(P<0.05)。结论 UCF-101神经保护作用可能与上调脑组织神经元XIAP蛋白的表达和抑制神经元的凋亡有关。

Objective To investigate the neuroprotective effect of 5-[5-（2-nitrophenyl）furfuryliodine]-l,3- diphenyl-2-thiobarbituric acid（UCF-101） on the cerebral neurons of rats during cerebral ischemia-reperfusion. 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 2h after the right middle cerebral artery occlusion. Rats were randomly divided into sham operated group, ischemia-reperfusion group and UCF-101 treated group. 24h after focal cerebral ischemiareperfusion, the infarct volume was calculated by TYC and TUNEL method was used to measure apoptotic neurons, and the expression of X-chromosome-linked inhibitor of apoptosis（XIAP） was detected by immunohistochemistry. Results No focal ischemia was found and very few TUNEL positive neurons were detected, and XIAP positive expression was shown in neuron in sham operated group. The distinct focal ischemia volumn was shown, the the number of TUNEL positive neurons was increased and the expression of XIAP was decreased in ischemia-reperfusion group than in sham operated group（P〈 0.05）. In UCF-101 treated group, the infarct volume and TUNEL positive neurons were decreased and XIAP expression increased comparing with the ischemia-reperfusion group（P〈0.05）. Conclusion The protective effect of UCF-101 treatment might be related to the increase of the expression of apoptotic inhibit protein XIAP and decrease of the quantity of the apoptosis neurons during the cerebral ischemia-repeffusion.