辛伐他汀对脑缺血-再灌注损伤大鼠周围血MIP-3α、BDNF、cleaved Caspase-3表达与mNSS的影响  

Effect of simvastatin on the expression of MIP-3α,BDNF,cleaved Caspase-3 and mNSS after cerebral ischemia-reperfusion injury in rats

作　　者：于春伟[1] 丛大忞[2] 杨春晓[3] 

机构地区：[1]哈尔滨医科大学附属第二医院肌电图室,黑龙江150086 [2]哈尔滨医科大学附属第二医院神经外科,黑龙江150086 [3]哈尔滨医科大学附属第二医院神经内科,黑龙江150086

出　　处：《脑与神经疾病杂志》2015年第5期358-362,共5页Journal of Brain and Nervous Diseases

摘　　要：目的通过观察辛伐他汀对脑缺血-再灌注损伤大鼠巨噬细胞炎性蛋白-3α(MIP-3α)、脑源性神经营养因子(BDNF)、活化的Caspase-3的表达及神经功能评分的影响,揭示辛伐他汀在促进脑缺血-再灌注损伤大鼠神经功能恢复中的作用。方法成年雄性Wistar大鼠60只,随机分为3组:缺血-再灌注损伤后辛伐他汀治疗组;缺血-再灌注损伤后生理盐水对照组;假手术组。每组各20只。采用Longa线栓法制作大鼠大脑中动脉缺血-再灌注模型,缺血2h后给予再灌注。治疗组缺血-再灌注损伤1d后口服辛伐他汀1mg·kg-1·d-1;对照组口服等量生理盐水;假手术组只分离血管。各组大鼠在治疗后1、3、5、7、14d进行神经功能评分(m NSS评分),检测血清中MIP-3α和BDNF的表达以及各组大鼠脑组织中活化的Capsase-3的表达。结果 m NSS评分结果显示在给药的前3d,治疗组与对照组相比神经功能恢复没有明显差别(P>0.05)。给药后第5天至第14天,治疗组神经功能恢复明显好于对照组(P<0.05)。血清中MIP-3α的表达结果显示,治疗组与对照组在给药后第1天没有明显差异,而从治疗的第3天开始直至实验结束。结论治疗组MIP-3α的水平始终低于对照组(P<0.05)。治疗组血清中BDNF的表达,给药后的第5天开始直至结束显著高于对照组(P<0.05)。治疗组在给药第3天和第5天后,脑组织中活化的Caspase-3表达低于对照组(P<0.05),而到给药第14天时这种差异不明显。Objective In this study , we investigated the neuroprotective property of simvastatin in middle cerebral artery occlusion （ MCAO ） induced ischemic rat model , by evaluating the expression levels of macrophage inflamma-3α（ MIP-3α） , brain-derived neurotrophic factor （ BDNF） , cleaved Caspase-3 and the score of neurological severity.Methods 60 adult Wistar rats were randomly divided into 3 groups： simvastatin treated group , saline control group and sham group .Focal cerebral ischemia was induced by occlusion of the left common carotid artery according to Longa ＇s suture method .reperfusion was performed after 2 hours of occlusion .Simvastatin was administered orally daily at a dose of 1 mg · kg · d-1 after the start of reperfusion .In saline control group an equivalent volume of normal saline was given at the same time points .The identical surgical procedure was performed in the sham group except the introduction of occlusion and reperfusion .Neurological motor measurement was evaluated using modified neurological severity scores （ mNSS） at 1, 3, 5, 7, 14 days after start of treatment .Expressions of MIP-3αand BDNF were detected by enzyme-linked immunosorbent assay （ ELISA ） , while expression of cleaved caspase-3 was measured by immunoblotting .Results The mNSS of simvastatin treated group was significantly lower than the control group from the fifth day to the fourteenth day （P〈0.05）.Started from the third day, expression of MIP-3αin simvastatin treated group significantly reduced compared to that in the control group （P〈0.05）.From the fifth day on, expression of BDNF in simvastatin treated group significantly increased than the control group （ P〈0.05） .On the third and the fifth day of treatment , the expression of cleaved caspas-3 in simvastatin treated group significantly decreased than the control group （P〈0.05）.Conclusion Taken together, our study demonstrate that simvastatin treatment could improve neurological function after ischemic insult .Its neur

关 键 词：辛伐他汀 巨噬细胞炎性蛋白-3α 半胱天冬酶-3 脑源性神经营养因子 脑缺血-再灌注损伤 

分 类 号：R743.32[医药卫生—神经病学与精神病学]