不同剂量蛋白酶体抑制剂对缺血后神经元的作用  

Effect of Different Dose of Proteasome Inhibitor on Neuron after Ischemic Stroke

作　　者：王中魁[1] 王卫[1] 魏东宁[1] 

机构地区：[1]解放军总医院第二附属医院,北京100091

出　　处：《中国医药导刊》2009年第12期2087-2089,共3页Chinese Journal of Medicinal Guide

摘　　要：目的:探索蛋白酶体抑制剂在不同剂量时对缺血后脑组织的作用及原因。方法:使用大鼠单侧大脑中动脉栓塞模型,50只大鼠随机分成5组,梗塞3小时后注入不同剂量的蛋白酶体抑制剂MG132,定时进行神经功能评分、TTC染色、TUNEL染色、Western blot检测Casepase 8蛋白表达。结果:MG132治疗有效缩小脑梗死体积,1mg/Kg组凋亡细胞数目最少,Casepase 8表达与MG132剂量相关。结论:蛋自酶体抑制剂对缺血区神经元的保护作用局限于低剂量效应,高剂量下对神经元有促凋亡作用。蛋白酶体抑制剂的保护作用可能通过Casepae 8途径起作用。Objective： To investigate the Protective Effect of different doses of Proteasome Inhibitor on Neuron after Isehemic Stroke. Methods：Fifty rats were randomly divided into five groups We determinod that a potent proteasorne inhibitor. MG132 exerted therapeutic effects in experimental model of middle cerebral artery occlusion. Either MG132 （0. 5. 1, 2 mg/kg） or vehicle was intravenously administered 3 h after stroke. The cerebral infarction tissues were stained by TTC and TUNEL. Western blot analysis was used to detect the expression level of Casepase 8. Results： MG132 at 0.1 mg/kg significantly reduced ischemic tissue volume compared to the controla The numbers of TUNEL cells in the ischemic regions were decreased subsequent to MG 132 treatments. MG132 induced a significant elevation of the expression level of Casepase 8. Conclusion： Proteasome Inhibitor protects neuron in ischemic tissue at a relatively low concentration, and it is toxic to neuron at a relatively high concentration. Proteasome Inbibitor protects neuron through Casepase 8 pathway

关 键 词：蛋白酶体抑制剂 脑梗死 Casepase 8 

分 类 号：R965[医药卫生—药理学]