阿替普酶改善局灶性脑缺血大鼠的认知功能

Improvement cognitive function in rats with focal cerebral ischemia by Alteplase

目的探讨阿替普酶改善大脑中动脉阻塞大鼠模型认知功能的机制。方法采用改良线栓法构建大脑中动脉左侧阻塞大鼠模型。将60只SD大鼠随机分成3组(每组20只):①假手术组采取假手术措施;②干预组于造模30 min后经尾静脉注射2μL浓度为10μg/μL的阿替普酶;③模型组受试大鼠经尾静脉注射2μL生理盐水。采用转角和前肢放置实验、Morris水迷宫实验、空间探索实验测定受试大鼠认知功能,采用ELISA法测定大鼠血脑屏障相关蛋白ZO-1及IL-6、TNF-α、Hs-CRP表达水平,采用Western法测定血脑屏障相关蛋白ZO-1蛋白表达水平。结果模型组、干预组受试大鼠右侧转角百分比明显高于假手术组,触须阳性百分比明显低于假手术组,干预组受试大鼠右侧转角百分比明显低于模型组,触须阳性百分比明显高于模型组(P<0.05)。模型组、干预组受试大鼠Morris水迷宫试验中平均逃避潜伏期明显高于假手术组,干预组明显低于模型组(P<0.05)。模型组、干预组受试大鼠空间探索实验中停留时间及穿越平台次数明显低于假手术组,干预组明显高于模型组(P<0.05)。模型组、干预组受试大鼠ZO-1蛋白表达水平明显低于假手术组,干预组明显高于模型组(P<0.05)。模型组、干预组受试大鼠IL-6、TNF-α、Hs-CRP表达水平明显高于假手术组,干预组明显低于模型组(P<0.05)。结论阿替普酶可有效改善大脑中动脉阻塞大鼠的认知功能,其机制可能与改善大鼠血脑屏障功能、控制其体内炎症反应、降低炎性因子表达水平相关。

Objective To investigate the effects of alteplase on blood brain barrier(BBB),inflammation and cognitive function in rats with middle cerebral artery occlusion(MCAO).Methods 60 SD rats were divided into randomly three groups(n=20).The rat model of middle cerebral artery occlusion was constructed by modified thread thrombus,and the control group took the sham operation.The intervention group injected 2μL amiperenzyme after the model 30 min,and the model group injected 2μL physiological saline.The rats′cognitive function was measured by the rotation angle and the experiment of forelimb placement,the Morris water maze experiment and the space exploration experiment.The expression level of ZO-1,IL-6,TNF-α,and Hs-CRP in rats was measured by ELISA.Determination of ZO-1 protein expression in bloodbrain barrier related protein by Western.Results The percentage of right turning angle in model group and intervention group was higher,and the percentage of positive tentacles was lower than control group.The percentage of right corner in intervention group was lower,and the percentage of positive tentacles was higher than model group(P<0.05).The average escape latency of the model group and intervention group was higher than control group,and the intervention group was lower than model group(P<0.05).The residence time and the number of crossing platform in model group and intervention group were lower than control group,and the intervention group was higher than model group(P<0.05).The expression level of ZO-1 protein in the model group and intervention group was lower than control group,and the intervention group was higher than model group(P<0.05).The levels of IL-6,TNF-αand Hs-CRP in model group and intervention group were higher than control group,while those in intervention group were lower than model group(P<0.05).Conclusion Alteplase can improve the cognitive function of rats with middle cerebral artery occlusion,the mechanism may be related to the improvement of the blood brain barrier,the control of the inflammatory response in the body,and the reduction of the expression of inflammatory factors.