柴胡加龙骨牡蛎汤对卒中后抑郁大鼠小胶质细胞极化及突触可塑性的影响  

Effects of Chaihu Plus Longgu Muli Decoction on Microglial Polarization and Synaptic Plasticity in Post-Stroke Depressed Rats

作　　者：刘元月 胡丹[1] 丁彩霞[1] 李传游[1] 肖婧[1] 李婷婷[1] 郭雪艳 盛蕾[1] LIU Yuan-yue;HU Dan;DING Cai-xia;LI Chuan-you;XIAO Jing;LI Ting-ting;GUO Xue-yan;SHENG Lei(The Second Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210017,China)

机构地区：[1]南京中医药大学第二附属医院,江苏南京210017

出　　处：《南京中医药大学学报》2023年第8期746-752,共7页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82205013);第四批全国西医学习中医优秀人才研修项目;江苏省第二中医院院内重点课题(SEZ202110,SEZ202012);南京中医药大学校自然科学基金(XZR2020050);江苏省第二中医院中青年科技菁英项目(SEZJY2023001)。

摘　　要：目的探讨柴胡加龙骨牡蛎汤对脑卒中后抑郁(PSD)模型大鼠行为学和小胶质细胞极化及神经突触可塑性的影响。方法将50只SD大鼠分为假手术组,模型组,柴胡加龙骨牡蛎汤低、中、高剂量组,大脑中动脉栓塞(MCAO)手术后进行慢性不可预知性温和应激(CUMS)4周,后进行柴胡加龙骨牡蛎汤治疗。治疗结束后进行Longa神经功能评分测定,通过糖水偏好测试和强迫游泳实验检测大鼠抑郁样表现,采用酶联免疫吸附测定法(ELISA)测定海马区炎症因子白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的表达水平,免疫荧光及蛋白免疫印迹法(Western blot)标记并定量大鼠海马区中CD16/CD32、CD206、突触后致密蛋白-95(PSD95)蛋白表达水平,透射电镜检测突触超微结构并可视化海马神经元的突触结构。结果与假手术组比较,模型组大鼠糖水偏好率降低(P<0.01),强迫游泳实验静止时间延长(P<0.01),海马区炎症因子IL-1β、IL-6和TNF-α的蛋白表达水平及M1表型CD16/CD32蛋白荧光强度升高(P<0.01),PSD-95、CD206蛋白水平明显降低(P<0.05,P<0.01),CD16蛋白水平升高(P<0.01);与模型组比较,柴胡加龙骨牡蛎汤中、高剂量组上述各指标均明显改善(P<0.05,P<0.01)。结论柴胡加龙骨牡蛎汤可以改善PSD模型大鼠的卒中后抑郁的相关行为学变化,其机制可能与调节小胶质细胞极化抗炎从而改善突触可塑性有关。OBJECTIVE To investigate the effects of Chaihu Plus Longgu Muli Decoction on behavior,microglial polarization and synaptic plasticity in post-stroke depression model(PSD)rats.METHODS 50 SD rats were divided into sham operation group,model group,and low,medium and high dose groups of Chaihu Plus Longgu Muli Decoction.After middle cerebral artery occlusion(MCAO)operation,chronic unpredictable mild stimulation(CUMS)was performed for 4 weeks,PSD model was established,and Chaihu Plus Longgu Muli Decoction was treated.After treatment,Longa nerve function score was measured,and depression-like manifestations were detected by sucrose preference test and forced swimming test.The expression levels of inflammatory factors interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)in hippocampus were determined by enzyme-linked immunosorbent assay(ELISA).The expression levels of CD16/CD32,CD206 and postsynaptic dense protein-95(PSD95)in the hippocampus of rats were labeled and quantified by immunofluorescence and Western blot.The synaptic ultrastructure was detected by radio microscopy and the synaptic structure was visualized.RESULTS Compared with the sham operation group,the sucrose preference rate of rats in the model group decreased(P<0.01),the static time of forced swimming experiment was prolonged(P<0.01),the expression levels of inflammatory cytokines IL-1β,IL-6 and TNF-αin the hippocampus region and the fluorescence intensity of CD16/CD32 protein in M1 phenotype were increased(P<0.01),PSD-95,CD206 protein levels were significantly decreased(P<0.05,P<0.01),CD16 protein level was increased(P<0.01).Compared with the model group,the above indexes in the medium and high dose groups of Chaihu Plus Longgu Muli Decoction were significantly improved(P<0.01).CONCLUSION Chaihu Plus Longgu Muli Decoction can improve the behavioral changes related to post-stroke depression in PSD model rats,and the mechanism may be related to the regulation of microglial polarization and anti-inflammato

关 键 词：卒中后抑郁 小胶质细胞 突触可塑性 柴胡加龙骨牡蛎汤 

分 类 号：R285.5[医药卫生—中药学]