利福平通过抑制蛋白激酶R活化调节鱼藤酮诱导的小胶质细胞炎症而发挥神经保护作用  

Rifampicin plays a neuroprotective role by inhibiting the activation of protein kinase R to regulate rotenone-induced microglial inflammation

作　　者：邓嘉强 井秀娜[1] 林淡钰[1] 卜璐璐 陈颖[1] 陶恩祥[1] DENG Jia-qiang;JING Xiu-na;LIN Dan-yu;BO Lu-lu;CHEN Ying;TAO En-xiang(Department of Neurology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,510120)

机构地区：[1]中山大学孙逸仙纪念医院神经内科,510120

出　　处：《岭南急诊医学杂志》2021年第2期121-124,共4页Lingnan Journal of Emergency Medicine

基　　金：国家自然科学基金(81571244);广东省基础与应用基础研发计划(2015A030310351);广东省重点领域研发计划项目(2018B0337001)。

摘　　要：目的:探讨利福平通过抑制蛋白激酶R(protein kinase R,PKR)活化对小胶质细胞炎症及其介导神经元凋亡的影响。方法:用鱼藤酮诱导BV2小胶质细胞构建PD炎症细胞模型,经利福平或者PKR抑制剂(C16)预先孵育2小时,Western blot检测p-PKR、PKR、NLRP3、Caspase-1、IL-1β等蛋白的表达量,流式细胞术(Flow cytometry)检测细胞凋亡率。结果:与鱼藤酮组相比,利福平预处理组和PKR抑制剂(C16)预处理组:p-PKR、NLRP3、IL-1β、Caspase-1蛋白表达水平出现下降(均P<0.05);共培养体系中SH-SY5Y细胞凋亡水平下降(均P<0.05)。结论:利福平可以抑制PD炎症细胞模型中PKR活化,减轻细胞炎症及介导神经元细胞凋亡。Objective:To explore the effect of rifampicin on microglia inflammation and cells apoptosis by inhibiting the activation of PKR in BV2 cells treated by rotenone. Methods:The PD inflammationcell model was established by rotenone in BV2 cells,before which rifampicin or PKR inhibitor(C16)was incubated for 2 hours. The protein expression levels of p-PKR,PKR,NLRP3,Caspase-1,IL-1β were detected by Western blot. The cells apoptosis was detected by Flow cytometry. Results:The protein expression levels of p-PKR,NLRP3,IL-1β and Caspase-1 which were pretreated with rifampicin(50 μmol/L)or C16(2 μmol/L)were significantly decreased(all P<0.05),compared with the rotenone group.Moreover,the apoptosis rate in rifampicin pretreatment group or C16 pretreatment group was lower than that in the rotenone group(all P<0.05). Conclusion:Rifampicin can suppressthe activation of PKRin the inflammatory cell model,whichcan alleviate cell inflammation and the apoptosis ratesmediated by the inflammation.

关 键 词：PKR 小胶质细胞 炎症小体 利福平 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]