阿托伐他汀对脑缺血再灌注大鼠血脑屏障的保护作用  

Protective effect of atorvastatin on blood brain barrier in rats with focal cerebral ischemia-reperfusion injury

作　　者：贺涓涓[1] 洪华[2] 杨世亮[2] 

机构地区：[1]中山大学附属第三医院康复医学科,广东广州510630 [2]中山大学附属第一医院神经内科,广东广州510080

出　　处：《中国病理生理杂志》2015年第2期219-223,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30971028);广东省自然科学基金资助项目(No.S2012010008539)

摘　　要：目的:研究在脑缺血再灌注(ischemia-reperfusion,IR)损伤中阿托伐他汀对血脑屏障的保护作用及相关机制。方法:SD大鼠72只随机分为3组:假手术组、IR组和阿托伐他汀组。阿托伐他汀组大鼠术后予以阿托伐他汀(20 mg·kg-1·d-1)灌胃治疗,每天1次,连续3 d。利用线栓法制作脑IR模型,缺血2 h后再灌注72 h,对各组大鼠的神经功能进行评分,并检测梗死侧大脑半球脑组织含水量、伊文思蓝(Evans blue,EB)渗出量、紧密连接相关蛋白occludin和炎症因子磷脂酰肌醇3-激酶p110γ(PI3K-p110γ)的表达水平。结果:与假手术组相比,IR组大鼠脑组织含水量、EB的渗出量及神经功能评分均增加(P<0.01),同时occludin表达下降(P<0.01),PI3Kp110γ表达增加(P<0.01);而阿托伐他汀治疗组大鼠脑水肿程度减轻(P<0.01),EB渗出量减少(P<0.01),occludin表达增加(P<0.01),PI3K-p110γ表达减少(P<0.01),神经功能评分下降,但差异无统计学意义(P>0.05)。结论:阿托伐他汀可以减轻脑IR损伤,可能与抑制炎症反应、增加紧密连接蛋白表达从而维持血脑屏障稳定性有关。AIM： To explore the protective effects of atorvastatin on blood brain barrier（ BBB） in cerebral ischemia-reperfusion（ IR） injury and the potential mechanisms involved. METHODS： SD rats were divided into sham group,IR group and atorvastain group. Intraluminal suture method was used to establish cerebral IR model,and the ischemic brain was reperfused for 72 h after the occlusion. The rats in atorvastatin group were administered with atorvastatin（ 20mg·kg- 1·d- 1） by gavage once a day for 3 consecutive days after operation. At 72 h after reperfusion,neurological function scores,the water content of the brain tissue,Evans blue（ EB） content of ischemic hemisphere,the expression of tight junction（ TJ）-associated protein occludin and inflammation factor phosphatidylinositiol 3-kinase-p110 gamma（ PI3Kp110γ） were tested and analyzed. RESULTS： In IR group,the rats showed elevated neurological function scores（ P〈0. 01）,brain tissue water content（ P〈0. 01） and EB content（ P〈0. 01）,accompanied with the down-regulation of occludin expression（ P〈0. 01） and up-regulation of PI3K-p110γ（ P〈0. 01） at 72 h after reperfusion. Compared with IR group,decreased brain edema（ P〈0. 01） and EB leakage（ P〈0. 01） were observed in atorvastatin group,accompanied with increased occludin expression（ P〈0. 01） and decreased PI3K-p110γ expression（ P〈0. 01）. However,no statistical difference of the neurological function scores between the 2 groups was observed. CONCLUSION： Atorvastain attenuates cerebral IR injury,which may be associated with the inhibition of inflammatory reactions and the up-regulation of TJ-associated proteins to maintain the stability of BBB.

关 键 词：脑缺血再灌注 阿托伐他汀 血脑屏障 

分 类 号：R363[医药卫生—病理学]