狗肝菜多糖抑制TLR-4/MyD88/NF-κB信号通路减轻急性肝衰竭  

Polysaccharides from Dicliptera chinensis (L.) Juss. attenuates acute liverfailure through inhibition of TLR-4/MyD88/NF-κB signalling pathway

作　　者：杨超越 钟明利[1] 曹后康 高雅[1,2] 张可锋 YANG Chao-yue;ZHONG Ming-li;CAO Hou-kang;GAO Ya;ZHANG Ke-feng;(Key Laboratory of Pharmacology for Prevention and Treatment of High Incidence Diseases in Guangxi Higher Education(Institutions,Guilin Medical University,Guilin Guangxi 541199,China;Guangxi Key Laboratory of Diabetic Systems Medicine,Guilin Guangxi 541199,China)

机构地区：[1]桂林医学院广西高校高发病防治药理学重点实验室,广西桂林541199 [2]广西糖尿病系统医学重点实验室,广西桂林541199

出　　处：《中国药理学通报》2025年第3期491-499,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82160811);广西省自然科学基金资助项目(No 2023GXNSFAA026220);广西糖尿病系统医学重点实验室开放课题(No GKLCDSM-20220101-01)。

摘　　要：目的基于TLR-4/MyD88/NF-κB信号通路,探讨狗肝菜多糖[polysaccharides from Dicliptera chinensis(L.)Juss.,DCP]对脂多糖(lipopolysaccharide,LPS)联合D-半乳糖胺(D-galactosamine,D-GalN)诱导的小鼠急性肝衰竭(acute liver failure,ALF),以及LPS诱导的RAW264.7细胞炎症反应的干预作用。方法小鼠随机分为对照组、模型组、水飞蓟素组、DCP低、中、高剂量组及毒性测试组。连续给药10 d后,注射LPS+D-GalN建立ALF模型。同时,用LPS刺激RAW264.7细胞建立炎症反应模型。结果生化检测显示,与模型组相比,DCP中、高剂量组小鼠血清ALT、AST、ALP、TBIL、γ-GT活性降低(P<0.05),肝脏中ROS、MPO、MDA含量减少(P<0.05),而SOD、GSH-Px、CAT活性增加,T-AOC水平升高(P<0.05);ELISA检测到肝脏中ICAM-1、VCAM-1、IL-6、IL-1β、TNF-α水平降低(P<0.05);HE染色显示,给予DCP后肝脏炎性细胞浸润减少,肝细胞坏死改善,DCP单独使用无明显器官毒性。qRT-PCR和Western blot结果表明,DCP抑制TLR-4/MyD88/NF-κB信号通路主要分子的表达(P<0.05);细胞验证实验也证实了该通路受DCP抑制。结论DCP通过抑制氧化应激和阻断TLR-4/MyD88/NF-κB信号通路减轻ALF。Aim To investigate the interventional effects of polysaccharides from Dicliptera chinensis(L.)Juss.(DCP)on acute liver failure(ALF)induced by lipopolysaccharide(LPS)combined with D-galactosamine(D-GalN)in mice,and on LPS-induced inflammatory responses in RAW264.7 cells,based on the TLR-4/MyD88/NF-κB signaling pathway.Methods Mice were randomly divided into the control,model,silymarin,DCP low,medium,and high dose groups,and toxicity test groups.After 10 consecutive days of treatment,ALF models were established by injecting mice with LPS+D-GalN.Additionally,an inflammatory response model was established by stimulating RAW264.7 cells with LPS.Results Biochemical assays showed that compared with the model group,the medium-and high-dose DCP groups exhibited decreased serum ALT,AST,ALP,TBIL,andγ-GT activities(P<0.05),reduced levels of ROS,MPO and MDA in liver(P<0.05),increased activities of SOD,GSH-Px,CAT,and elevated T-AOC levels(P<0.05).ELISA revealed lower levels of ICAM-1,VCAM-1,IL-6,IL-1β,and TNF-αin liver(P<0.05).HE staining indicated reduced inflammatory cell infiltration and improved hepatocyte necrosis in liver after DCP administration.The use of DCP alone showed no significant organ toxicity.qRT-PCR and Western blot results indicated that DCP inhibited the expression of key factors in TLR-4/MyD88/NF-κB signaling pathway(P<0.05).Cell validation experiments also confirmed that this pathway was inhibited by DCP.Conclusion DCP alleviates ALF primarily by inhibiting oxidative stress and blocking the activation of the TLR-4/MyD88/NF-κB signaling pathway.

关 键 词：狗肝菜多糖 脂多糖 D-半乳糖胺 急性肝衰竭 氧化应激 TLR-4/MyD88/NF-κB信号通路 炎症反应 

分 类 号：R-332[医药卫生] R284.1R322.47R364.5R575.3