海马p75神经营养因子受体在老年小鼠术后认知障碍中的作用  

Role of hippocampal p75 neurotrophin receptor in postoperative cognitive dysfunction of aged mice

作　　者：高玉竹 纪木火 周志强 GAO Yuzhu;JI Muhuo;ZHOU Zhiqiang(Department of Anesthesiology,Jinling Hospital,School of Medicine,Nanjing University,Nanjing 210002,China)

机构地区：[1]南京大学医学院临床学院/东部战区总医院麻醉科,江苏南京210002 [2]南京医科大学附属第二医院麻醉科,江苏南京210002

出　　处：《中风与神经疾病杂志》2021年第12期1072-1075,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金面上项目(81571083)。

摘　　要：目的探讨海马p75NTR在老年小鼠术后认知障碍(POCD)中的作用及其机制。方法老年雄性C57BL/6小鼠30只,采用剖腹探查术建立POCD动物模型,随机分为3组(n=10):对照组、手术组及手术+TAT组。造模结束后第5天进行旷场实验,检测小鼠的运动距离及中心区域的活动时间。造模结束后第6~7天行条件恐惧实验,检测环境和声音诱发僵直时间。行为学结束后取海马组织,使用Western blot测p75NTR、BDNF、PSD95、Trk B及pCREB表达情况,使用免疫荧光检测海马caspase-3阳性细胞数,使用高尔基染色法比较海马CA;区突触数目。结果与对照组相比,手术组场景僵直时间均显著降低(P<0.05);与手术组比较,手术+TAT组场景僵直时间显著升高(P>0.05)。与对照组相比,手术组海马p75NTR与caspase-3阳性细胞数表达显著增加,而BDNF、PSD95、Trk B及pCREB表达显著降低,同时CA;区树突棘量减少(P<0.05);与手术组比较,手术+TAT组海马caspase-3阳性细胞数减少,而BDNF、PSD95及pCREB的表达水平以及CA;区的树突棘数量显著增加。结论p75NTR在老年小鼠POCD中发挥关键作用。Objective To investigate the role of the p75 neurotrophic receptor(p75NTR)in the cognitive impairment induced by laparotomy surgery of aged mice,and to explore the possible mechanism.Methods Thirty eighteenmonth-old male mice were equally randomized into three groups(n=10):control group,surgery group,surgery+TAT group.Open field test was performed 5 days after the surgery to record the exploration distance and the time in the center.Fear-conditioned training was performed 6 days after the surgery,and fear-conditioned test was performed 7 days after the surgery to record the freezing time.The hippocampus was harvested immediately after the behavioral test.Western blot was applied to detect the levels of p75NTR,BDNF,PSD95,Trk B and pCREB in the hippocampus,immunofluorescence was applied to detect the number of caspase-3 positive cells in the hippocampus,and Golgi staining was applied to observe the changes of dendritic spines in hippocampal CA;region.Results In the open field test,the total distance and the time in the center had no significant difference among the three groups(P>0.05).In the fear conditioning test,compared with control group,the percentage of the contextual conditional freezing time decreased significantly in surgery group(P<0.05),and the expressions of BDNF,PSD95,Trk B and pCREB and the number of dendritic spines in CA;were significantly decreased(P<0.05),the expression of p75NTR and the number of caspase-3 positive cells were increased significantly in the surgery group(P<0.05).Compared with the surgery group,the percentage of the contextual conditional freezing time increased significantly in surgery+TAT group,and the expressions of BDNF,PSD95,Trk B,and pCREB and the number of dendritic spines in CA;were significantly increased,the number of caspase-3 positive cells were decreased significantly in the surgery+TAT group(P<0.05).Conclusion Hippocampal p75NTR plays a key role in the pathophysiology of POCD.

关 键 词：老年 术后认知功能障碍 海马 P75NTR 

分 类 号：R749.1[医药卫生—神经病学与精神病学]