CXCL7/CXCR2轴调控突触可塑性在肥胖相关认知功能障碍中的作用  

Effect of CXCL7/CXCR2 axis on synaptic plasticity in obesity-related cognitive dysfunction

作　　者：胡佳 许傲雪 胡锐 薛琦 黄春霞[1] 张野[1] HU Jia;XU Ao-xue;HU Rui;XUE Qi;HUANG Chun-xia;ZHANG Ye(Dept of Anesthesiology and Perioperative Medcine,the Second Hospital of Anhui Medical University,Key Laboratory of Anesthesiology and Perioperative Medcine of Anhui Higher Education Institutes,Anhui Medical University,Hefei 230601,China)

机构地区：[1]安徽医科大学第二附属医院麻醉与围术期医学科,麻醉与围术期医学安徽普通高校重点实验室,安徽合肥230601

出　　处：《中国药理学通报》2024年第5期881-886,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学青年基金项目(No 82300945);安徽省自然科学基金面上项目(No 2308085MH260);安徽医科大学校科研基金项目(No 2022xkj040);国家自然科学基金孵育计划(No 2022GQFY07)。

摘　　要：目的从动物和细胞两个层面探讨趋化因子配体7[chemokine(C-X-C motif)ligand 7,CXCL7]/趋化因子受体2(CXCR2)轴在肥胖相关认知功能障碍中的作用机制。方法高脂饮食诱导的肥胖模型(diet-induced obesity,DIO),采用新物体识别实验检测认知水平;免疫荧光染色法观察海马小胶质细胞、星形胶质细胞的活化水平以及小鼠突触后密度蛋白95(postsynaptic density protein 95,PSD95)的含量。采用ELISA法测定海马组织CXCL7的含量;高尔基染色法测定海马神经元树突棘密度。其次,分别使用重组小鼠CXCL7和干扰CXCR2表达的si-RNA处理HT22小鼠海马神经元细胞系。用细胞免疫荧光染色法观察HT22细胞的CXCL7和PSD95的表达水平。结果与Ctrl组小鼠比较,DIO组小鼠在新物体识别实验中的辨别指数明显降低;伴有海马小胶质细胞、星形胶质细胞的活化水平明显升高,PSD95的含量减少,神经元的树突棘密度降低,CXCL7的含量明显升高。与DIO组小鼠相比,AWL组小鼠在新物体识别实验中的辨别指数明显升高。与Ctrl组细胞比,Ctrl+CXCL7组的PSD95水平降低;与Ctrl+CXCL7组细胞比,si-CXCR2+CXCL7组的PSD95水平升高。结论高脂饮食诱导肥胖小鼠的中枢神经炎症,进而引起认知功能障碍,可能是与CXCL7/CXCR2轴介导的突触可塑性改变有关。Aim To explore the effect of CXCL7/CXCR2 axis on obesity-related cognitive dysfunction at both animal and cellular levels.Methods The novel object recognition test was performed to assess the cognition.After the preparation of the frozen sections,the activation of microglia and astrocytes in hippocampi and the level of PSD95 were determined by immunofluorescence staining.The content of CXCL7 in hippocampi was determined by enzymelinked immunosorbent assay.The dendritic spine density of hippocampal neurons was observed by Golgi staining.Furthermore,HT22 cells were treated with the recombinant mouse CXCL7 and/or si-RNA targeting CXCR2.After the treatment,the levels of CXCL7 and PSD95 were observed by immunocytochemistry staining.Results Compared with animals in the control group,there was significantly decreased discrimination index,increased activation of microglia and astrocytes,decreased content of PSD95,decreased density of dendritic spine,and increased content of CXCL7 in hippocampi in the DIO group.Compared with animals in the DIO group,there were significantly increased discrimination index in the AWL group.In HT22 cells,the level of PSD95 significantly decreased in the Ctrl+CXCL7 group compared with the control group.This decrease was attenuated in the si-CXCR2+CXCL7 group compared with the Ctrl+CXCL7 group.Conclusion Chronic high-fat diet induces neuroinflammation and subsequently induces cognitive dysfunction,which may be related to the synaptic plasticity mediated by the CXCL7/CXCR2 axis.

关 键 词：CXCL7 CXCR2 肥胖 认知功能障碍 神经炎症 

分 类 号：R-332[医药卫生] R322.81R338.64R392.11R589.2R741