M1型小胶质细胞极化在大脑皮层梗死后继发丘脑损伤中的作用  

Effect of M1 microglial polarization on secondary damage in the thalamus after cerebral cortical infarction

作　　者：石喆[1,2] 左夏林 彭林辉 卢志伟[1,2] 李孔平 SHI Zhe;ZUO Xialin;PENG Linhui;LU Zhiwei;LI Kongping(Department of Neurology,the Affiliated Brain Hospital,Guangzhou Medical University,Guangzhou 510370,Guangdong,China;Key Laboratory of Neurogenet-ics and Channelopathies of Guangdong Province and the Ministry of Education of China,Guangzhou Medical Uni-versity,Guangzhou 510260,Guangdong,China;不详)

机构地区：[1]广州医科大学附属脑科医院神经内科,广东广州510370 [2]广东省神经科学疾病研究重点实验室、神经致病基因和离子通道教育部重点实验室,广东广州510260 [3]广州医科大学附属第二医院神经科学研究所,广东广州510260

出　　处：《实用医学杂志》2024年第22期3138-3145,共8页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81971233);广州市科技计划项目(编号:2023A04J1203);广州医科大学科研能力提升项目(编号:2023-2024)。

摘　　要：目的探讨M1型小胶质细胞极化在大脑皮层梗死后继发丘脑损伤中的作用。方法使用电凝法制备成年雄性SD大鼠的局灶性皮层梗死模型,并将其随机分为假手术组和术后1~4周的不同时间点模型组。在评估各组大鼠神经功能改变的基础上,通过免疫组织化学和免疫荧光分别检测丘脑VPN区NeuN、GFAP、Iba-1和Iba-1^(+)/CD68^(+)(M1型小胶质细胞)及Iba-1^(+)/CD206^(+)(M2型小胶质细胞)阳性细胞数量和形态变化;通过免疫印迹检测丘脑VPN区IL-1β、TNF-α、IL-10和Arg-1表达水平。结果与假手术组相比,模型组4周时NeuN免疫阳性细胞减少(P<0.05),GFAP和Iba-1免疫阳性细胞增多(P<0.05),促炎因子TNF-α和IL-1β表达明显升高(P<0.05),神经功能学评分显著升高(P<0.05)。与M2型小胶质细胞相比,模型组4周梗死同侧丘脑VPN区M1型小胶质细胞显著增多(P<0.05)。结论M1型小胶质细胞极化可能参与了大脑皮层梗死后同侧丘脑损害的过程。Objective To explore the effects of M1 polarization of microglia on secondary damage in the thalamus after cerebral cortical infarction.Methods A focal cortical infarct model of adult male SD rats was pre-pared using eletrocoagulation and randomized into Sham and model groups at different time points 1~4 weeks after surgery.Based on the assessment of neurofunctional changes in each group of rats,immunohistochemistry was used to observe the number and morphology of NeuN,GFAP and Iba-1 positive cells in(Ventral posterior nucleus of thalamus,VPN)of the ipsilateral thalamus after distal middle cerebral artery occlusion(dMCAO).Immunofures-cence was used to detect the number and morphology of M1 microglia marker(Iba-1^(+)/CD68^(+)cells)and M2 microg-lia marker(Iba-1^(+)/CD206^(+)cells)in VPN of the ipsilateral thalamus after dMCAO.Western blot was used to detect the expression levels of IL-1β,TNF-α,IL-10 and Arg-1 in VPN of the ipsilateral thalamus after dMCAO.Results The results of immunohistochemistry showed a significant decrease in NeuN positive cells and an increase in the density of GFAP and Iba-1 in the ipsilateral VPN of rats after dMCAO when compared with Sham group(P<0.001).Compared with sham group,the protein levels of TNFαand IL-1βwere elevated in the ipsilateral VPN elevated(P<0.05).In addition,the model group rats exhibited higher Bederson scores,beam-walking test and adhesive removal test scores after dMCAO compared with Sham group(P<0.05).The numbers of M1 microglia marker(Iba-1^(+)/CD68^(+)cells)were significantly increased when compared with M2 microglia marker(Iba-1^(+)/CD206^(+)cells)in ipsilateral VPN of rats after dMCAO.Conclusion M1 polarization of microglia may play an essential role in secondary damage of thalamus after cerebral cortical infarction.

关 键 词：脑梗死 远隔损害 丘脑 小胶质细胞极化 神经炎症 

分 类 号：R651.15[医药卫生—外科学]