Notch1通路对雷公藤甲素致肝毒性的的保护作用研究  

Protective Effect of Notch1 Pathway on Triptolide Induced Hepatotoxicity

作　　者：袁淑芳 刘志娟[1] 李俩 何唐艳 麻芝英 张月圆 柯柳[1] 佘东明[1] Yuan Shufang;Liu Zhijuan;Li Lia;He Tangyan;Ma Zhiying;Zhang Yueyuan;Ke Liu;She Dongming(People's Hospital of Liuzhou,Liuzhou,545006)

机构地区：[1]广西柳州市人民医院,柳州545006

出　　处：《基因组学与应用生物学》2020年第8期3763-3770,共8页Genomics and Applied Biology

基　　金：柳州市人民医院院内科研基金项目(lry202006)资助。

摘　　要：雷公藤甲素是传统中草药雷公藤的主要活性成分,具有多种药理作用,但其严重的不良反应(尤其是肝毒性)限制了雷公藤甲素的临床应用。本研究为探讨Notch1信号转导对雷公藤甲素诱导肝毒性的潜在保护作用。本研究以张氏肝细胞为体外模型,研究Notch1信号转导在雷公藤甲素诱导肝毒性中的作用。结果发现雷公藤甲素引起张氏肝细胞的氧化应激和细胞凋亡,并伴随着Notch1激活信号的抑制。此外,Jagged1激活Notch1可以防止雷公藤甲素诱导的细胞毒性,而DAPH对Notch1的抑制则使损伤加重。这些结果表明,Notch1信号转导通路通过降低氧化应激和下调凋亡来改善雷公藤甲素的有害效应,Notch1的激活可能提供一种新的治疗策略来保护雷公藤甲素诱导的肝毒性。Triptolide(TP),the predominant active component of the traditional Chinese herb Tripterygium wilfordii Hook f.has been shown to exert multiple pharmacological effects.However,the clinical applications of TP are limited by its severe adverse effects,especially hepatotoxicity.In order to investigate the potential protective effects of Notch1 on TP-induced hepatotoxicity.In this study,the role of Notch1 signal transduction in triptolide induced hepatotoxicity was studied using Chang liver cells as an in vitro model,TP caused oxidative stress and cellular apoptosis in Chang liver cells,which were accompanied by inhibition of the Notch1 activation signal in this results.In addition,the activation of Notch1 by Jagged1 protected against TP-induced cytotoxicity,whereas the inhibition of Notch1 by DAPT increased the damage.Overall,these results suggested that Notch1 signaling ameliorated the detrimental effects of TP by decreasing oxidative stress and downregulating apoptosis,and activation of Notch1 may provide a novel therapeutic strategy to protect against triptolide induced hepatotoxicity.

关 键 词：雷公藤 雷公藤甲素 NOTCH1 氧化应激 细胞凋亡 

分 类 号：R285[医药卫生—中药学]