HMGB1、S100B和RAGE的表达与大鼠脑缺血后认知功能障碍发生的关系  

Correlation Between HMGB1/RACE and S100B/RAGE Expression and Cognitive Dysfunction of Rats Induced by Brain Ischemia

作　　者：李秀菊 王成夭[2] 夏颖[3] 咸淑悦 李心怡[2] 马敏[2] 潘霞[2] 

机构地区：[1]武汉市第八医院麻醉科,湖北武汉430010 [2]武汉大学中南医院麻醉科,湖北武汉430071 [3]湖北省妇幼保健院,湖北武汉430070

出　　处：《武汉大学学报（医学版）》2016年第2期205-208,共4页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:ZRY1010);湖北省卫生厅资助项目(编号:JX4B23)

摘　　要：目的:评价高迁移率族蛋白1(HMGB1)、S100B和糖基化终末产物受体(RAGE)的表达与大鼠脑缺血后认知功能障碍发生的关系。方法:雄性SD大鼠48只,3-4月龄,体重250-300g,采用随机数字表法,将其分成2组(n=24):假手术组(SH组)和脑缺血组(BI组)。通过阻断双侧颈总动脉(CCA)及椎动脉血流成功建立了四血管闭塞法大鼠全脑缺血模型,分别于术后1、3、5和7d时,每组取6只大鼠,采用Y迷宫测试认知功能,记录正确反应次数和全天总反应时间;分别于上述时点认知功能测试结束后,处死3只大鼠,取海马组织,采用Western blot法测定海马CA1区HMGB1、S100B和RAGE的蛋白表达;处死余3只大鼠,取脑组织,荧光共聚焦显微镜下观察HMGB1、S100B和RAGE共表达情况。结果:与SH组比较,BI组术后1、3、5、7d认知功能明显均出现减退,表现为站立次数和正确反应次数减少,全天总反应时间明显增加(P<0.01)。与SH组比较,BI组大鼠海马HMGB1、S100B和RAGE蛋白表达在术后1d明显增加(P<0.01);术后7d,则基本恢复至对照组水平。免疫荧光实验显示HMGB1和RAGE主要在海马CA1区呈锥体细胞层表达,S100B主要在海马CA1区呈放射性表达。与SH组比较,BI组术后1、3和5d,大鼠海马CA1区HMGB1、S100B和RAGE阳性细胞计数显著增加(P<0.01);术后7d,基本恢复至正常对照组水平。结论:大鼠脑缺血后认知功能障碍发生只可能与海马CA1区的HMGB1、S100B和RAGE表达上调有关。Objective： To evaluate the correlation between HMGB1/RACE and S100B/RAGE expression and cognitive dysfunction of rats induced by brain ischemia. Methods： Forty-eight male SD rats, aged 3-4 months, weighing 250-300 g, were randomly divided into 2 groups （n=24 each） ： group sham operation （group SH） and group chronic brain ischemia （group BI）. The brain ischemia models were made by permanent ligation of bilateral common carotid arteries. And cognitive func- tion was assessed by using Y maze test on the 3rd, 5th and 7th day after operation. The expres- sions of HMGB1/RAGE, S100B/RAGE were detected by Western Blot. The colocalizations of HMGB1/RAGE,S100B/RAGE were observed by double immunofluorescent staining. Results： Compared with group SH, group BI significantly decreased the number of grid cross, the rearing and correct responses and increased the time the animals spent in the central square and total reac tion as compared with group SH （P〈0.01）. The HMGB1, S100 and RAGE expressions signifi- cantly increased on the 1st, 3rd and 5th day after operation in group BI as compared with group SH （P〈0.01）, and decreased to the level of group SH on the 7th day. The immunofluorescence expression of HMGB1, S100B, RAGE and positive cells count showed that HMGB1 and RAGE were mainly expressed in pyramidal cell layer of hippocampus CA1 area, S100B was mainly ex- pressed radioactively in hippoeampal CA1 area. Compared with group SH, the immunofluores- cence expressions of HMGB1, S100B, RAGE and positive cells count of group BI significantly in- creased on the 1st, 3rd, 5th day after operation （P〈0.01）, and decreased to the level of group SH on the 7th day. Conclusion： Brain ischemia induced cognitive dysfunction may be related to the HMGB1/RACE and S100B/RAGE expression in hippocampus.

关 键 词：脑缺血 认知障碍 高迁移率族蛋白质类 S100蛋白质类 糖基化终末产物 

分 类 号：R614.2[医药卫生—麻醉学]