依那西普对大鼠脑缺血再灌注损伤及MMP-9、Claudin-5表达的影响  

Effect of etannercept on ischemia reperfusion injury and experssion of MMP-9、Claudin-5 in rats suffering ischemia-reperfusion injury

作　　者：刘琳[1] 包正军[2] 谭利明[1] 周道[1] 

机构地区：[1]中南大学湘雅二医院神经内科,长沙硕士研究生410011 [2]中南大学湘雅医院株洲临床学院

出　　处：《卒中与神经疾病》2013年第1期7-11,共5页Stroke and Nervous Diseases

摘　　要：目的探讨依那西普对大鼠脑缺血再灌注损伤的保护作用及机制。方法线栓法制作大鼠大脑中动脉缺血再灌注(MCAO)模型,大鼠随机分为正常组、假手术组、模型组和依那西普低、中、高剂量组。每组大鼠再随机分为3组,分别在再灌注1、2、5d处死。利用干湿重法测脑组织含水量,免疫组化法检测缺血脑组织基质金属蛋白酶-9(MMP-9)和紧密连接相关蛋白-5(claudin-5)蛋白的表达水平变化。结果与假手术组比较,模型组大鼠各时间点脑含水量明显升高,MMP-9表达水平升高、Claudin-5表达水平降低(P<0.05);与模型组比较,依那西普各剂量组脑含水量、MMP-9表达水平明显降低,Claudin-5表达水平明显升高(P<0.05),且随剂量的增加,大鼠脑含水量、MMP-9表达水平明显降低,Claudin-5表达水平明显升高(P<0.05)结论依那西普注射液对大鼠脑缺血再灌注损伤后血脑屏障有一定的保护作用,其作用机制可能与降低MMP-9、增加claudin-5的表达水平,从而维持血脑屏障的稳定性有关。Objective To study protective effects of etanercept on cerebral ischemia-reperfusion injury. Methods Rat model of cerebral ischemia reperfusion injury was created by the middle cerebral artery occlusion （MCAO）. SD rats were randomized into 4 groups： the normal group, sham-operation group, ischemia- reper- fusion group, and etanercept treatment group. And then etanercept treatment group were divided into low- dose, middle-dose and high-dose group. Each group was equally divided into subgroups and rats were killed at 1d, 2d and 5d after reperfusion, respectively. The dry weight method was used to evaluate brain water content of the ischemic side and the expressions of matrix metalloproteinase-9 （MMP-9） and claudin-5 were investiga- ted with immunohistochemistry. Results Compared with sham operation group, the brain water content and the expression of MMP-9 increased while the expression of Claudin-5 decreased significantly in model group af- ter reperfusion（P〈0. 05） ;compared with model group, the brain water content and the expression of MMP-9 decreased while the expression of Claudin-5 increased in etanercept groups after reperfusion （P〈 0. 05） ; and with increasing doses of etanercept, the brain water content and the expression of MMP-9 decreased signifi- cantly while the expression of Claudin-5 increased in etanercept group（P〈0. 05）. Conclusions The present study provides in vivo evidence that etanercept can protect against cerebral ischemia reperfusion injury. The mechanism is related to maintaining the stability of the blood-brain barrier by decreasing the cerebral levels of MMP-9 and increasing the levels of claudin-5.

关 键 词：脑缺血再灌注损伤 肿瘤坏死因子-α 依那西普 血脑屏障 MMP-9 CLAUDIN-5 

分 类 号：R743[医药卫生—神经病学与精神病学]