强力霉素抑制MMP-9对大鼠局灶性缺血再灌注脑损伤的保护作用  

Doxycycline-mediated inhibition of MMP-9 protects focal cerebral ischemia-reperfusion injury in rats

作　　者：焦海霞[1,2] 王萍[1] 马腾[1] 薛一雪[1] 

机构地区：[1]中国医科大学基础医学院神经生物学教研室,沈阳110001 [2]福建医科大学基础医学院生理学与病理生理学系,福州350004

出　　处：《第三军医大学学报》2010年第24期2591-2594,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(3087265630973079);教育部高等学校博士学科点专项科研基金(20092104110015);沈阳市科学技术计划项目(1091175-1-01;1081266-9-00)~~

摘　　要：目的观察强力霉素对脑缺血再灌注MMP-9活性的影响,探讨其对神经元的保护作用。方法利用大脑中动脉线栓法(middle cerebral artery occlusion,MCAO)制备局灶性脑缺血再灌注模型,SD大鼠分为假手术组、生理盐水组、强力霉素组,每组18只。激光多普勒血流仪分别检测大鼠手术前、MCAO时、再灌注24 h大脑中动脉脑血流;再灌注24 h时应用TTC染色法观察大鼠脑梗死体积;明胶酶谱法检测缺血区脑组织MMP-9活性变化;透射电镜观察缺血区脑组织神经元超微结构。结果生理盐水组与强力霉素组大鼠在再灌注24 h时脑血流[分别为基础值的(57.98±4.20)%、(59.23±3.30)%]与MCAO时[分别为基础值的(22.94±3.16)%、(21.63±3.46)%]差异显著(P<0.01),但在同一时间点两组间无显著差异(P>0.05);强力霉素组大鼠脑梗死体积[(9.77±2.68)%]与生理盐水组[(33.44±4.50)%]相比显著减少(P<0.01);生理盐水组大鼠MMP-9活性(5.95±0.73)与假手术组(1.21±0.15)相比显著升高(P<0.01),应用强力霉素后MMP-9活性(2.47±0.42)与生理盐水组相比显著降低(P<0.01);生理盐水组大鼠神经元超微结构发生异常改变,强力霉素组大鼠神经元形态结构基本正常。结论强力霉素抑制MMP-9活性对大鼠局灶性缺血再灌注损伤脑组织具有保护作用。Objective To observe the activity alteration of MMP-9,and investigate the protective effect of doxycycline on brain tissue after cerebral ischemia-reperfusion injury in rats.Methods Cerebral ischemia-reperfusion model was induced by middle cerebral artery occlusion（MCAO）.SD rats were divided into sham-operated group,saline group and doxycycline group,18 rats in each group.The laser-doppler probe was fixed before and after operation（MCAO）,and at reperfusion 24 h,to measure local cerebral blood flow（CBF） in an area supplied by the middle cerebral artery.The infarct volume was defined by 2,3,5-triphenyltetrazolium chloride（TTC） staining at reperfusion 24 h.Gelatin zymography was used to determine the activity of MMP-9 in the cerebral ischemic tissue.Neuron ultrastructure was investigated by transmission electron microscopy（TEM） in the rat ischemic cerebral cortex.Results There was significant change between the cerebral blood flow（CBF） [（57.98±4.20）%,（59.23±3.30）% respectively of the base line] at reperfusion 24 h and MCAO [（22.94±3.16）%,（21.63±3.46）% of the base line]（P0.01）,but no significant difference was seen between the saline and doxycycline groups at same time point（P0.05）.The cerebral infarction volume in doxycycline group [（9.77±2.68）%] was significantly decreased than that in saline group [（33.44±4.50）%]（P0.01）.The activity of MMP-9 in saline group（5.95±0.73） were significantly increased compared with the sham-operation group（1.21±0.15） at reperfusion 24 h（P0.01）.Doxycycline（2.47±0.42） significantly inhibited the enhanced activity of MMP-9 at reperfusion 24 h（P0.01）.Neuron ultrastructure was abnormal change in saline group,but there was obvious recovery for the abnormal neuron ultrastructure in doxycycline group.Conclusion Doxycycline exerts a protective effect on focal cerebral ischemia-reperfusion injury in rats by inhibiting MMP-9 activity.

关 键 词：强力霉素 脑缺血 再灌注 基质金属蛋白酶 脑梗死 

分 类 号：R345.5[医药卫生—基础医学] R743.31