姜黄素对急性缺血性脑卒中小鼠MCP-1和CCR2水平的影响  

Effect of curcumin on chemoattractant protein-1 and C-C chemokine receptor 2 levels in acute ischemic stroke mice

作　　者：张鑫[1,2] 薛慧 孟天予[2] 耿尚勇 郑雅楠[2] 赵吉利[1] 杜文倩 ZHANG Xin;XUE Hui;MENG Tianyu(Baotou Medical College,Inner Mongolia University of Science&Technology,Baotou 014040,China)

机构地区：[1]内蒙古科技大学包头医学院,内蒙古包头014040 [2]包头市中心医院,内蒙古包头014040

出　　处：《中风与神经疾病杂志》2023年第4期345-349,共5页Journal of Apoplexy and Nervous Diseases

基　　金：内蒙古自然科学基金项目(2019MS08207)。

摘　　要：目的小胶质细胞介导的神经炎症在急性缺血性脑卒中(acute ischemic stroke,AIS)的发病机制中起着至关重要的作用。单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)的激活在多种神经系统疾病中发挥促炎作用。本研究旨在探讨姜黄素在CIS后的抗炎作用及其对MCP-1/CCR2信号通路的影响。方法采用烧灼法建立永久、局灶性脑梗死模型(dMCAO)。雄性C57BL/6小鼠随机分为假手术组、对照组和姜黄素组。假手术组仅分离颈总动脉且不灼烧大脑中动脉分支。姜黄素组于dMCAO术后连续7 d给予腹腔注射CUR[200 mg/(kg·d)],对照组腹腔注射等体积溶剂二甲基亚砜(DMSO)。TTC染色方法计算脑梗死体积,转棒实验(Rota-rod)及Longa评分评价小鼠肢体功能。Western blot及免疫荧光技术检测MCP-1、CCR2的表达水平,Elisa法检测TNF-α、IL-1β、IL-6表达水平。结果AIS后MCP-1/CCR2表达增加。在实验中,与Sham组相比,dMCAO组表现出更高的改良Longa评分、更短的滚轮运动时间、更低的脑血流量减少百分比和更大的梗死面积(P<0.05);CUR组较dMCAO组的改良Longa评分更低,Rota-rod运动时间更长,脑血流量减少百分比更高,梗死面积更小(P<0.05)。姜黄素治疗改善了小鼠近期神经功能转归,减少了梗死周围区域Iba-1的合成,抑制了IL-1β、TNF-α和IL-6等促炎因子的合成。结论姜黄素通过下调MCP-1/CCR2通路抑制AIS后神经炎症反应,减轻神经功能缺损。姜黄素可能为AIS患者提供一种有前景的治疗策略。Objective To investigate the neuroprotective effects of curcumin(CUR)on acute ischemic stroke(AIS)mice and to determine its effects on monocyte chemoattractant protein-1(MCP-1)and C-C chemokine receptor 2(CCR2)expression levels.Methods A permanent,focal cerebral infarction(dMCAO)model was established by cautery.Male C57BL/6 mice were randomly divided into a sham-operated(Sham),control(dMCAO),and CUR group.In the Sham group,only the common carotid artery was isolated and the middle cerebral artery branches were not cauterized.The CUR group was intraperitoneally administered CUR(200 mg/kg·d)for 7 consecutive days after dMCAO,and the dMCAO group was intraperitoneally administered an equal volume of solvent dimethyl sulfoxide.Cerebral infarct volume was calculated by the 2,3,5-triphenyltetrazolium chloride staining method,limb function was evaluated by the Rota-rod and Longa score.Western blot and immunofluorescence techniques were used to assess MCP-1 and CCR2 expression levels,and enzyme-linked immunosorbent assay(ELISA)was used to measure tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and IL-6 expression levels.Results In the experiment,the dMCAO group showed higher modified Longa scores,shorter times on the roller,and larger infarct areas than the Sham group;the CUR group showed lower modified Longa scores,longer times on the Rota-rod,and smaller infarct areas than that of the dMCAO group.Western blot and immunofluorescence results showed that the expression of microglia,MCP-1,and CCR2 was significantly downregulated,and ELISA results showed that the expression levels of TNF-α,IL-1β,and IL-6 in mouse brain tissue were decreased.Conclusion CUR has a protective effect on AIS mice,and CUR can downregulate the expression of MCP-1 and CCR2 in mouse brain tissues,reduce the release of inflammatory factors,and exert its physiological functions.

关 键 词：急性缺血性卒中 姜黄素 单核趋化因子-1 趋化因子受体2 

分 类 号：R743.3[医药卫生—神经病学与精神病学]