天然产物研究与开发 ›› 2017, Vol. 29 ›› Issue (3): 472-476.doi: 10.16333/j.1001-6880.2017.3.020

• 开发研究 • 上一篇    下一篇

雷公藤甲素致小鼠肝损伤的机制研究

于淑静,魏彩冰,陶崑*,周莲娣*   

  1. 重庆医科大学分子医学与肿瘤研究中心基础医学院免疫学教研室,重庆 400016
  • 出版日期:2017-03-31 发布日期:2017-04-06

Mechanism of Triptolide-induced Liver Injury

YU Shu-jing,WEI Cai-bing,TAO Kun*,ZHOU Lian-di*   

  1. Research Center of Molecular Medicine and Cancer,College of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China
  • Online:2017-03-31 Published:2017-04-06

摘要: 本文研究雷公藤甲素致肝损伤作用机制。将雌性C57BL/6小鼠20只随机分为2组,并以雷公藤甲素造模,通过检测血清中谷丙转氨酶(ALT)水平变化,以及观察小鼠肝脏组织切片HE染色结果,了解肝脏损伤情况;RT-PCR法检测小鼠肝脏中白细胞介素(IL)-17、IL-6、维甲酸孤儿核受体(ROR-γt)mRNA表达水平,ELISA法检测IL-17、IL-6蛋白表达水平,Western blot法检测小鼠肝脏中TLR4蛋白表达水平。与对照组比较,雷公藤甲素模型组小鼠血清ALT水平显著升高(P<0.005),HE染色切片显示较多的肝细胞坏死和炎症细胞浸润,IL-17、IL-6、ROR-γt mRNA表达水平和IL-17、IL-6蛋白表达水平显著升高(P<0.005),此外,TLR4蛋白表达水平显著升高(P<0.005)。结果表明,雷公藤甲素所导致的肝损伤可能通过激活TLR4信号,增加IL-17、IL-6的表达,影响Th17特异性转录因子ROR-γt,进而促进Th17细胞活化,增强其致炎功能。

关键词: 雷公藤甲素, 肝损伤, 炎症因子, C57BL/6小鼠

Abstract: In this study,the mechanism of triptolide(TP)-induced liver injury was investigated.A total of 20 female C57BL/6 mice were randomly divided into two groups.Serum alanine aminotransaminase(ALT) levels and hepatic pathological change were used to explore the degree of liver damage,and hepatitic interleukin(IL)-17,IL-6 were detected through RT-PCR and ELISA.The mRNA expression of hepatic retinoid related orphan receptor(ROR-γt) was also examined by RT-PCR.The expression of hepatic Toll-like receptor4(TLR4) was examined by Western blot.Data showed that TP effectively increased serum ALT levels(P<0.005, vs control group) and promoted hepatic pathological damage.Meanwhile,TP also significantly promoted the expression of IL-17,IL6,ROR-γt mRNA and IL-17,IL-6 protein in mouse liver(P<0.005).Furthermore,the protein expression of TLR4 was obviously increased,compared with control group(P<0.005).Taken together,the result suggested that TP induced liver injury through activating the TLR4 signal,increasing the expression of IL-17,IL-6 and Th17 specific transcription factor ROR-γt,and promoting the activation of Th17 cells and enhancing the inflammatory function.

Key words: triptolide, liver injury, cytokines, C57BL/6 mouse

中图分类号: 

R967