雷公藤甲素对Con A诱导小鼠急性肝损伤的保护作用及机制  

Protective Effect and Mechanisms of Triptolide on Acute Liver Injury Induced by Concanavalin A in Mice

作　　者：卫博文 蒋杨雨 曹丹 冯婧 田雷喻 李健 WEI Bo-wen;JIANG Yang-yu;CAO Dan;FENG Jing;TIAN Lei-yu;LI Jian(Department of Histology and Embryology,School of Traditional Chinese Medicine,BUCM,Beijing,102488,China;The medical experimental teaching center,School of Traditional Chinese Medicine,BUCM,Beijing,102488,China)

机构地区：[1]北京中医药大学中医学院组胚教研室,北京102488 [2]北京中医药大学中医学院教学实验中心,北京102488

出　　处：《现代生物医学进展》2021年第14期2607-2616,共10页Progress in Modern Biomedicine

基　　金：国家自然科学基金面上项目(81873099)。

摘　　要：目的:探究雷公藤甲素(Triptolide)对刀豆蛋白A(Concanavalin, Con A)诱导的小鼠急性肝损伤的保护机制。方法:雄性BALB/c小鼠30只,随机等分为正常对照组、Con A模型组和雷公藤甲素治疗组。通过尾静脉注射Con A构建小鼠急性肝损伤模型。微孔板法检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平,HE染色观察肝组织病理变化,免疫组化、实时荧光定量PCR(RT-qPCR)和酶联免疫吸附试验(ELISA)检测肝组织及血清中细胞因子水平。结果:与正常对照组比较,Con A诱导急性肝损伤小鼠血清ALT、AST水平显著增高(P<0.05),肝组织呈局灶性炎性浸润、坏死。与Con A模型组比较,雷公藤甲素治疗组小鼠血清ALT、AST水平显著下降(P<0.05);肝组织病理程度明显减轻;肝组织中CD4+T细胞的浸润降低,促炎细胞因子(IFN-γ、TNF-α、IL-1β、IL-2)的水平显著降低(P<0.05)。结论:雷公藤甲素可以通过抑制CD4+T细胞向肝脏募集,下调IFN-γ、TNF-α、IL-1β、IL-2的表达,有效防治Con A诱导的急性免疫性肝损伤。Objective: To investigate the protective mechanism of Triptolide on acute liver injury induced by Concanavalin(Con A) in mice. Methods: Thirty male BALB/c mice were randomly divided into Normal control group, Con A model group and Triptolide treatment group. A mouse model of acute liver injury was constructed through tail vein injection of Con A. Microplate method to detect serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels, HE staining to observe liver tissue pathological changes, immunohistochemistry, real-time fluorescent quantitative PCR(RT-qPCR) and enzyme-linked immunosorbent assay(ELISA)Detect cytokine levels in liver tissue and serum. Results: Compared with that in the Normal control group, Con A induced a significant increase in serum ALT and AST levels in mice with acute liver injury(P<0.05), and liver tissue showed focal inflammatory infiltration and necrosis. Compared with that in the Con A model group, the serum ALT and AST levels of the mice in the Triptolide treatment group were significantly decreased(P<0.05);The liver tissue pathology was significantly reduced;The CD4+T cell infiltration in the liver tissue was reduced, and the proinflammatory cytokines(The levels of IFN-γ, TNF-α, IL-1β, IL-2) were significantly reduced(P<0.05).Conclusion: Triptolide can effectively prevent Con A-induced acute immune liver injury by inhibiting the recruitment of CD4+T cells to the liver, down-regulating the expression of IFN-γ, TNF-α, IL-1β, and IL-2.

关 键 词：雷公藤甲素 刀豆蛋白A 急性肝损伤 

分 类 号：R-33[医药卫生] R575