长春西汀抑制小胶质细胞M1/M2型极化改善慢性脑缺血大鼠认知功能及神经元损伤  

Vinpocetine inhibits M1/M2 polarization of microglia and improves cognitive function and neuronal damage in rats with chronic cerebral ischemia

作　　者：陈鑫[1] 王旭[1] 姜童子 CHEN Xin;WANG Xu;JIANG Tong-zi(Department of Neurology,Shenyang First People’s Hospital,Shenyang 110041;Department of Respiratory and Critical Care,Qingdao Central Hospital,Qingdao 261500,China)

机构地区：[1]沈阳市第一人民医院神经内科,辽宁沈阳110041 [2]青岛市中心医院呼吸与危重症科,山东青岛261500

出　　处：《解剖科学进展》2022年第1期46-50,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(20180551091)。

摘　　要：目的探讨长春西汀抑制小胶质细胞极化改善慢性脑缺血大鼠认知功能的作用机制。方法将30只SD大鼠随机分为假手术组(sham)、模型组(model)及长春西汀组(Vin),每组10只,采用双侧颈总动脉结扎法复制慢性脑缺血大鼠模型,长春西汀组术后腹腔注射长春西汀10 mg/kg,共计28d。Morris水迷宫检测认知功能;HE染色观察大鼠海马区病变;免疫荧光染色检测微管相关蛋白2(MAP-2);ELISA测定各组大鼠脑组织匀浆中白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)及肿瘤坏死因子-α(TNF-α)含量;免疫荧光染色检测M1型小胶质细胞极化标志物Iba-1/iNOS和M2型小胶质细胞极化标志物Iba-1/Arg1;Western blot检测Notch/Jagged通路相关蛋白Notch-1、NICD、Rbp-Jk及Jagged-1的表达。结果与模型组相比,长春西汀显著改善大鼠认知功能,改善大鼠海马区病理损伤,显著增加海马区神经元数量,显著降低大鼠脑内IL-1β与TNF-α水平,显著增加大鼠脑内IL-10水平;显著降低Iba-1/iNOS细胞数量,显著增加Iba-1/Arg1细胞数量;此外,长春西汀还可显著降低Notch-1、NICD、Rbp-Jk及Jagged-1蛋白表达。结论长春西汀可通过抑制Notch/Jagged通路促进M1型小胶质细胞向M2型转换,减轻神经元损伤,从而改善慢性脑缺血大鼠认知功能。Objective To explore the effects of leukotriene receptor antagonist on oxidative stress and nerve cell apoptosis in rats with spinal cord injury and its possible mechanism.Methods Thirty SD rats were randomly divided into sham group(sham),model group(model)and vinpocetine group(Vin),with 10 rats in each group.The chronic cerebral ischemia rats model was induced by bilateral common carotid artery permanent occlusion.Mice in vinpocetine group were intraperitoneally injected with vinpocetine 10 mg/kg for 28 days.Cognitive function was evaluated by Morris water maze.The pathological changes in the hippocampus of rats were observed by HE staining.The microtubule-associated protein 2(MAP-2)expression was observed by immunofluorescence staining.Contents of interleukin-1β(IL-1β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were detected by ELISA.The polarization markers Iba-1/iNOS of M1-type microglia and Iba-1/Arg1 of M2-type microglia was observed by immunofluorescence staining.The expression of Notch-1,NICD,Rbp-Jk and Jagged-1 was detected by Western blot.Results Compared with the model group,vinpocetine significantly improved the cognitive function and pathological damage in the hippocampus,significantly increased the number of neurons in the hippocampus,significantly decreased the levels of IL-1βand TNF-α,and significantly increased the level of IL-10 in the brain of rats.The number of Iba-1/iNOS cells was significantly decreased,and the number of Iba-1/Arg1 cells was significantly increased.In addition,vinpocetine significantly reduced the expression of Notch-1,NICD,RBP-Jk,and Jagged-1.Conclusion Vinpocetine can promote the transition of M1 microglia to M2 by inhibiting the Notch/Jagged pathway,reduce neuronal damage,and thus improve cognitive function in rats with chronic cerebral ischemiay.

关 键 词：长春西汀 慢性脑缺血 小胶质细胞 神经元 Notch/Jagged通路 

分 类 号：R651.15[医药卫生—外科学]