大鼠脑缺血模型中基质金属蛋白酶2/9活化增加及紧密连接蛋白逐渐降解  

The increased activation of matrix metalloproteinase 2/9 and gradual degradation of claudin in rat models of middle cerebral artery ischemia

作　　者：梁佳[1] 戚智锋[2] 师文娟[2] 刘克建[2] 

机构地区：[1]辽宁医学院科学实验中心,辽宁省锦州市121001 [2]首都医科大学宣武医院脑血管病研究所,北京市100053

出　　处：《中国组织工程研究》2015年第27期4322-4327,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81171242);辽宁医学院校长基金项目资助(XZJJ20140105)~~

摘　　要：背景:在脑卒中后急性期脑损伤过程中,基质金属蛋白酶破坏血管基膜的完整性,促进中性粒细胞和炎性因子的迁移,引起继发性脑损伤。目的:观察大鼠局部脑缺血模型中不同缺血时间下基质金属蛋白酶2/9活性及紧密连接蛋白的降解规律。方法:将39只雄性SD大鼠随机均分为3组,采用改良线栓法建立大脑中动脉缺血(脑卒中)模型,即分离颈外动脉,采用经颈外动脉插入线栓进入颈内动脉最终到达大脑中动脉的方法,3组缺血时间分别为3,5,7 h,再灌注后2 h,测试各组Zea-Longa和Ludmila Belayev神经功能学评分,脑组织梗死面积、基质金属蛋白酶2/9活性及紧密连接蛋白5的降解。结果与结论:随着缺血时间的延长,脑梗死面积逐渐增大,组间两两比较差异有显著性意义(P<0.05);随着缺血时间的延长,中枢神经系统损伤逐渐加重,组间两两比较差异有显著性意义(P<0.05);随着缺血时间的延长,基质金属蛋白酶2/9的活性逐渐增强,组间两两比较差异有显著性意义(P<0.05);随着缺血时间的延长,紧密连接蛋白5的表达逐渐减少。说明长时间缺血后,脑组织的进行性损伤引起基质金属蛋白酶2/9活化的逐渐增加及紧密连接蛋白5的逐渐降解。BACKGROUND： During the process of acute brain injury after stroke, matrix metalloproteinase can undermine the integrity of vascular basement membrane, promote the migration of neutrophils and inflammatory factors, and cause secondary brain injury. OBJECTIVE： To investigate the activation of matrix metalloproteinase 2/9 and the degradation rule of claudin in rat models of middle cerebral artery ischemia at different ischemic durations. METHODS： Thirty-nine male SD rats were randomly divided into three groups according to different ischemicdurations（3, 5 and 7 hours）. Middle cerebral artery occlusion（stroke） model was established using modified suture method, i.e., separation of the external carotid artery, inserting the suture into the internal carotid artery through the external carotid artery, and eventually reaching the middle cerebral artery. The ischemic duration in these three groups was respectively 3, 5 and 7 hours. After 2 hours of reperfusion, Zea-Longa score and Ludmila Belayev score, brain infarct area, matrix metalloproteinase 2/9 activities and claudin 5 degradation were determined in each group. RESULTS AND CONCLUSION： With the extension of ischemic duration, brain infarct area gradually increased, central nervous system damage gradually aggravated, matrix metalloproteinase 2/9 activities gradually increased, and claudin-5 expression gradually decreased. There were significant differences between any two ischemic durations in terms of each of above-mentioned indices. The results indicate that after long duration of ischemia, the progressive damage of brain tissue can cause the gradual increase of activation of matrix metalloproteinase 2/9 and the gradual degradation of claudin 5.

关 键 词：脑缺血 基质金属蛋白酶2 基质金属蛋白酶9 紧密连接蛋白 实验动物 脑及脊髓损伤动物模型 脑缺血模型 紧密连接蛋白5 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]