THIP对MK-801介导小鼠脑脱髓鞘损伤的保护作用  

The Protective Effect of THIP on MK-801-mediated Brain Demyelination Injury in Mice

作　　者：李金霞 王聃 韩勇 尚彤 刘娟[1] 马全瑞[1] LI Jinxia;WANG Dan;HAN Yong;SHANG Tong;LIU Juan;MA Quanrui(Department of Human Anatomy and Histo-Embryology,School of Basic Medicine,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院人体解剖与组织胚胎学系,银川750004

出　　处：《宁夏医科大学学报》2023年第5期433-438,共6页Journal of Ningxia Medical University

基　　金：宁夏医科大学颅脑疾病重点实验室开放课题(LNKF202103)。

摘　　要：目的 探究γ-氨基丁酸(GABA)A受体(GABAAR)选择性激动剂加波沙朵(THIP)对地卓西平马来酸盐(MK-801)介导小鼠脑髓鞘损伤后小鼠认知障碍、髓鞘损伤和少突胶质细胞(OLs)分化的保护作用。方法 将36只C57BL/6J小鼠随机分为对照组(Blank组)、MK-801损伤组(MK-801组)和THIP干预组(MK-801+THIP组),每组12只。采用腹腔注射MK-801的方法制备MK-801脑损伤模型,MK-801组小鼠连续14 d腹腔注射MK-801,MK-801+THIP组小鼠在第8天添加THIP直至造模结束,Blank组腹腔注射相同剂量生理盐水。利用水迷宫实验检测小鼠学习记忆功能的改变;电镜观察髓鞘超微结构的改变;免疫荧光实验检测成熟少突胶质细胞(OLs)(CC-1+/Olig2+)数量的改变;利用Western blot检测少突胶质细胞分化调控蛋白GPR17的改变。结果 水迷宫实验结果显示,MK-801组小鼠学习记忆功能受损,MK-801+THIP组小鼠学习记忆功能有改善(P均<0.05);电镜结果显示,MK-801组小鼠髓鞘板层结构松散,MK-801+THIP组小鼠髓鞘板层结构致密;免疫荧光结果显示,MK-801组较Blank组成熟OLs(CC-1+/Olig2+)数量减少,MK-801+THIP组较MK-801组成熟OLs(CC-1+/Olig2+)数量增多(P均<0.05);Western blot结果显示,MK-801组较Blank组GPR17表达升高,MK-801+THIP组较MK-801组GPR17表达降低(P均<0.01)。结论 THIP可改善MK-801诱导的脑损伤模型小鼠学习记忆功能及髓鞘损伤程度,可能与其影响OLs分化有关。Objective To investigate the protective effect of gaboxadol(THIP),a selective agonist of GABA A receptor(GABAAR),on cognitive impairment,myelin injury and oligodendrocytes(OLs)differentiation in model mice mediated by dizocilpine maleate(MK-801).Methods A total of 36 C57BL/6J mice were randomly divided into the control group(Blank group),the MK-801 group and the THIP treatment group(MK-801+THIP group),with 12 mice in each group.In this study,MK-801 mediated brain injury model was prepared by intraperitoneal injection of MK-801.The mice in the MK-801 group were intraperitoneally injected with MK-801 for 14 consecutive days.The mice in the MK-801+THIP group were intraperitoneally injected with MK-801 for 8 consecutive days and then THIP was delivered at the same time,until the end of modeling.The same dose of normal saline was intraperitoneally injected into the mice of Blank group.The changes in mice learning and memory were observed by water maze experiment.The ultrastructural changes of myelin sheath were observed by electron microscopy.The changes in the number of mature oligodendrocytes(OLs)(CC-1+/Olig2+)were detected by immunofluorescence double labeling.Western blot was used to detect the protein expression of GPR17,a negative regulatory marker in the differentiation stage of OLs.Results The results of water maze test showed that the learning and memory function of MK-801 group mice was impaired while it was improved in MK-801+THIP group(P all<0.05).The results of electron microscopy showed that the myelin lamellar structure of the MK-801 group was loose while it was dense in MK-801+THIP group.Immunofluorescence results showed that the number of mature OLs(CC-1+/Olig2+)in MK-801 group was lower than that in Blank group,the number of mature OLs(CC-1+/Olig2+)in MK-801+THIP group was higher than that in MK-801 group(P all<0.05).Western blot results showed that the protein expression of GPR17 in MK-801 group was higher than that in Blank group,the expression of GPR17 in MK-801+THIP group was lower than that in M

关 键 词：髓鞘 少突胶质细胞 地卓西平马来酸盐 Γ-氨基丁酸A受体 加波沙朵 

分 类 号：R749.3[医药卫生—神经病学与精神病学]