摘要
目的探讨消退素D1(resolvin D1,RvD1)是否通过甲酰肽受体2(formyl peptide receptor 2,FPR2)调节小胶质细胞极化,减轻脑缺血/再灌注后的炎症损伤。方法运用线栓法建立大脑中动脉栓塞(MCAO)模型,将造模后的大鼠随机分为模型组(MCAO),RvD1组和RvD1联合FPR2抑制剂Boc-2(RvD1+Boc-2)组,另设假手术(Sham)对照组。脑缺血后24 h,运用TTC染色法检测脑梗死体积和免疫荧光法检测髓过氧化物酶(MPO),免疫荧光双染法进行标记FPR2/Iba-1、CD16/Iba-1和CD206/Iba-1的表达,RT-qPCR法检测M1型释放的TNF-α、iNOS、IL-1β和M2型释放的Arg-1、TGF-β1、IL-10 mRNA的表达。结果RvD1明显减少脑梗死体积和MPO的表达,并且其受体FPR2在小胶质细胞上表达。RvD1降低M1型CD16+/Iba-1+细胞数和TNF-α、IL-1β、iNOS mRNA的表达,增加M2型CD206+/Iba-1+细胞数和TGF-β1、IL-10、Arg-1 mRNA的表达,联合使用FPR2抑制剂Boc-2后RvD1的这些作用都受到抑制。结论RvD1通过FPR2可以改善脑缺血/再灌注后炎症损伤,其作用与调控激活的小胶质细胞从M1型向M2型方向极化有关。
Aim To investigate whether RvD1 regulates microglial polarization through FPR2 and allevi-ates the inflammatory damage after cerebral ischemia-reperfusion.Methods The middle cerebral artery occlusion(MCAO)model was established by Longa method.The rats after MCAO were randomly divided into:model group,RvD1 group and RvD1+Boc-2 group,and a sham-operated group was set up as control as well.Cerebral infarct volume was measured,MPO activities in rat brain were measured by immunofluorescence.The expression and localization of FPR2/Iba-1,CD16/Iba-1 and CD206/Iba-1 were detected by immunofluorescence double labeling method.The expressions of TNF-α,IL-1βand iNOS in M1 and TGF-β,IL-10,Arg-1 in M2 were detected by RT-qPCR.Results RvD1 significantly reduced cerebral infarction volume and the expression of MPO,and its receptor FPR2 was expressed in microglia.RvD1 down-regulated M1 markers CD16+/Iba-1+cells and the mRNA expression of TNF-α,IL-1β,iNOS,and up-regulated M2 markers CD206+/Iba-1+cells and the mRNA expressions of TGF-β1,IL-10,Arg-1.The effect of RvD1 was partially blocked by Boc-2(FPR2 antagonist).Conclusions RvD1 can reduce inflammation via FPR2 after ischemic-reperfusion injury,and its mechanism may be related to promotion of the polarization of the microglia from M1 to M2.
作者
刘玉莲
巫芳华
杨开令
周颖
高宇容
刘微
LIU Yu-lian;WU Fang-hua;YANG Kai-ling;ZHOU Ying;GAO Yu-rong;LIU Wei(Basic Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2021年第6期791-797,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81673772)
广州中医药大学“青年英才培养工程”项目(No QNYC20170102)。