利福平对鱼藤酮诱导小胶质细胞caspase-1活性的影响  

Effects of rifampicin on caspase-1 activation in rotenone-induced microglia

作　　者：梁嫣然[1] 井秀娜[1] 林淡钰[1] 陈颖[1] 毕伟[2] 曾志芬[1] 伍霞[1] 陶恩祥[1] 

机构地区：[1]中山大学孙逸仙纪念医院神经内科,广州510120 [2]暨南大学附属第一医院神经内科,广州510630

出　　处：《中华脑科疾病与康复杂志（电子版）》2015年第4期36-40,共5页Chinese Journal of Brain Diseases and Rehabilitation（Electronic Edition）

基　　金：国家自然科学基金(81371391);广东省医学科研基金(B2014130);国家级大学生创新创业训练计划项目(201410558098);广东省自然科学基金(2014A030313202);广东省公益研究与能力建设专项资金项目(2014A020212164)

摘　　要：目的探讨利福平对鱼藤酮诱导的BV2小胶质细胞产生炎症反应的影响及相关机制。方法将经过利福平预处理的BV2小胶质细胞加入鱼藤酮刺激,用Real-time PCR以及酶联免疫吸附试验(ELISA)法检测接受药物处理后小胶质细胞产生IL-1β的变化;采用caspase-1活性检测试剂盒检测小胶质细胞内caspase-1的活性,流式细胞术检测细胞凋亡率。用SPSS 16.0统计软件进行统计分析,计量资料使用均数±标准差(x珋±s)表示,多组间比较采用单因素方差分析,两两比较采用LSD-t检验,P<0.05说明差异有统计学意义。结果与鱼藤酮组相比,50μmol/L利福平预处理组可明显降低小胶质细胞内鱼藤酮介导的炎症因子IL-1β的基因表达(t=4.11,P<0.05)和上清液中IL-1β的分泌(t=35.81,P<0.05),并显著抑制caspase-1的活性(t=11.62,P<0.05)。将BV2小胶质细胞与PC12细胞用Transwell体系共培养,利福平预处理组(25、50μmol/L)和caspase-1抑制剂组的PC12细胞的细胞凋亡率均低于鱼藤酮组,差异有统计学意义(t值分别为3.82、7.98、10.12,均P<0.05)。结论利福平可能通过抑制caspase-1活化对抗鱼藤酮刺激下小胶质细胞产生的炎症毒性。Objective To investigate the effect of rifampicin on inflammatory reaction in rotenone-treated BV2 cells.Methods After pre-incubation with rifampicin ,BV2 cells were treated with rotenone .The mRNA and protein levels of IL-1βwere estimated by real-time PCR and ELISA,the activation of caspase-1 was detected by caspase-1 activity assay kit ,and the cell apoptosis was assessed by flow cytometry .SPSS 16.0 was used for statistical analysis and the data were presented as x-＆#177;s.The comparison among groups was analyzed using One-way analysis of variance （ ANOVA） followed by LSD-t test,and P〈0.05 indicated that the difference was statistically significant .Results Compared with rotenone group , pretreatment with rifampicin（50 μmol/L）could significantly inhibit the gene expression and protein levels of IL-1β（t=4.11, 35.81,both P〈0.05）,and significantly suppress the activity of caspase-1（t=11.62,P〈0.05）.Moreover, after co-incubation of BV2 microglial cells in transwell system ,apoptosis rates of PC12 cells in rifampicin pretreatment groups（25 and 50 μmol/L） and caspase-1 inhibitor group were lower than in rotenone group , and the differences were statistically significant （t values were 3.82,7.98,and 10.12,respectively,all P〈0.05）.Conclusion Rifampicin may protect BV2 cells against inflammation induced by rotenone via suppressing activation of caspase-1.

关 键 词：帕金森病 利福平 白细胞介素1Β 炎症 小神经胶质细胞 

分 类 号：R742.5[医药卫生—神经病学与精神病学]