CBR2激活与小胶质细胞的活化和损伤的关系

目的：探讨大麻素CBR2受体激动剂AM1241预处理对脂多糖（LPS）和γ-干扰素（IFN-γ）所致炎症反应对小胶质细胞活化和损伤的影响。方法：联用LPS和IFN-γ作为小胶质细胞损伤模型,将细胞分为Control组、AM1241组、LPS/IFN-γ组和AM1241＋LPS/IFN-γ组;AM1241组和AM1241＋LPS/IFN-γ组经AM1241预处理2h,LPS/IFN-γ组和AM1241＋LPS/IFN-γ组用含LPS和IFN-γ的培养基培养24h。采用MTT法检测细胞代谢率,硝酸还原酶法检测细胞培养液中一氧化氮（NO）释放量,酶联免疫吸附剂测定细胞培养基中炎症因子释放量,倒置相差显微镜观察细胞形态。结果：与LPS/IFN-γ组相比,AM1241＋LPS/IFN-γ组细胞代谢率明显升高（P〈0.05）,NO、TNF-α、IL-1β和IL-10释放量明显减少（P〈0.05）,活化和损伤程度明显减轻。结论：大麻素CBR2受体激动剂AM1241预处理可减轻LPS和IFN-γ对小胶质细胞的活化和损伤。

The relationship between CBR2 Activation and Injury Induced by Inflammation

Objective：To investigate the effects of cannabinoid CBR2 receptor agonist AM1241 preconditioning on microglia activation and injury induced by lipopolysaccharide（LPS） plus interferon-γ（IFN-γ）.Methods：LPS plus IFN-γ was used to induce inflammation.MTT assay was used to find a suitable AM1241 concentration for preconditioning.Cells were pretreated with medium containing different AM1241 concentrations,from 0μM to 10μM;5μM was chosen for next steps.Then cells were assigned to control group,AM1241 group,LPS/IFN-γ group and AM1241＋LPS/IFN-γ group.After AM1241 pretreatment,the medium of 4 groups were changed with normal medium.2h later,the medium of Control and AM1241 groups were changed with normal medium again and cul-tured for 24h.The medium of LPS/IFN-γ and AM1241＋ LPS/IFN-γ groups were changed with medium containing LPS and IFN-γ.Cells were cultured for 24h.Microglial metabolism was assessed by MTT assay;NO release was measured by Reagent Kit;The concen-trations of inflammatory factors（TNF-α,IL-1β and IL-10） were detected by enzyme linked immunosorbent assay reagent kit（ELISA）;Microglial shapes were observed through microscope.Results：cell metabolism of AM1241 group was higher than that of the Control group significantly（P0.05）;AM1241 group released less NO,TNF-α,IL-1β and IL-10 than that of LPS/IFN-γ group（P0.05）.Conclusion：Cannabinoid CBR2 receptor agonist AM1241 preconditioning reduces microglial activation and injury induced by inflam-mation.