吴茱萸碱调节HMGB1/TLR4/NF-κB信号通路对百草枯中毒大鼠肝损伤的影响  

Effects of evodiamine on liver injury in rats with paraquat poisoning by regulating the HMGB1/TLR4/NF-κB signaling pathway

作　　者：刘红玲 杨莉[1] 王健[1] LIU Hong-ling;YANG Li;WANG Jian(Emergency Department of the First Affiliated Hospital of Henan University of Science and Technology,Luoyang(Luoyang Henan,471000),China)

机构地区：[1]河南科技大学第一附属医院急诊科,河南洛阳471000

出　　处：《中西医结合肝病杂志》2024年第11期996-1000,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：河南省医学科技攻关计划项目(No.LHGJ20190564)。

摘　　要：目的:探讨吴茱萸碱(EVO)对百草枯(PQ)中毒大鼠肝损伤及高迁移率族蛋白1/Toll样受体4/核因子-κB(HMGB1/TLR4/NF-κB)信号通路的影响。方法:将大鼠分为对照组(Control组)、百草枯染毒组(PQ组)、吴茱萸碱低、高剂量处理组(EVO-L、EVO-H组)、吴茱萸碱高剂量处理+HMGB1重组蛋白组(EVO-H+r-HMGB1组);ELISA检测血清中肝功能指标谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)水平和炎症因子肿瘤坏死因子-a(TNF-a)、白介素-1β(IL-1β)及氧化应激指标超氧化物歧化酶(SOD)及丙二醛(MDA)水平;HE染色观察各组大鼠肝组织病理变化并进行肝组织学评分;Western blot检测HMGB1、TLR4、p-NF-κB p65/NF-κB p65表达。结果:PQ组较Control组肝小叶中央静脉淤血增多,肝细胞水肿坏死及肝细胞浆空泡化明显,核固缩且伴有明显的炎症浸润,病理学评分、ALT、AST、TBil、TNF-α、IL-1β、MDA水平及HMGB1、TLR4、p-NF-κB p65/NF-κB p65表达升高,SOD水平降低(P<0.05);EVO-L、EVO-H组较PQ组肝小叶中央静脉淤血减少,肝细胞浆空泡化减轻,水肿减轻,炎症浸润减少,病理学评分、ALT、AST、TBil、TNF-α、IL-1β、MDA水平及HMGB1、TLR4、p-NF-κB p65/NF-κB p65表达降低,SOD水平升高(P<0.05);EVO-H+r-HMGB1组较EVO-H组肝组织病理损伤加重,病理学评分、ALT、AST、TBil、TNF-α、IL-1β、MDA水平及HMGB1、TLR4、p-NF-κB p65/NF-κB p65表达升高,SOD水平降低(P<0.05)。结论:吴茱萸碱可改善百草枯中毒大鼠肝损伤,其作用机制与抑制HMGB1/TLR4/NF-κB通路有关。Objective:To investigate the effects of evodiamine(EVO)on liver injury and high mobility group protein-B1/Toll-like receptor 4/nuclear factor-κB(HMGB1/TLR4/NF-κB)signaling pathway in rats with paraquat(PQ)poisoning.Methods:The rats were grouped into a control group,a paraquat poisoning group(PQ group),a low and high dose evodiamine group(EVO-L,EVO-H groups),and a high-dose evodiamine+HMGB1 recombinant protein group(EVO-H+r-HMGB1 group).The ELISA was applied to detect liver function indicators such as alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil)levels,inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and oxidative stress indicators such as superoxide dismutase(SOD)and malondialdehyde(MDA)levels in serum.The HE staining was applied to observe the pathological changes in liver tissue of rats in each group and liver histological scoring was performed.The Western blot was applied to detect the expression of HMGB1,TLR4,and p-NF-κB p65/NF-κB p65.Results:Compared with the control group,the PQ group showed an increase in central venous congestion in the hepatic lobules.Obvious edema and necrosis of liver cells,vacuolization of liver cytoplasm,nuclear pyknosis,and obvious inflammatory infiltration,the pathological scores,ALT,AST,TBil,TNF-α,IL-1β,MDA levels,and HMGB1,TLR4,p-NF-κB p65/NF-κB p65 expression elevated,SOD level decreased(P<0.05).Compared with the PQ group,the EVO-L and EVO-H groups showed a decrease in central venous congestion in the liver lobules,a reduction in vacuolization of liver cytoplasm,a reduction in edema,and a reduction in inflammatory infiltration,the pathological scores,ALT,AST,TBil,TNF-α,IL-1β,MDA levels,and HMGB1,TLR4,p-NF-κB p65/NF-κB p65 expression reduced.Also,the SOD level increased(P<0.05).The pathological damage to liver tissue in the EVO-H+r-HMGB1 group was more severe than that in the EVO-H group,the pathological scores,ALT,AST,TBIL,TNF-α,IL-1β,MDA levels,and HMGB1,TLR4,p-NF-κB p65/NF-κB p65 express

关 键 词：吴茱萸碱 高迁移率族蛋白1/Toll样受体4/核因子-κB信号通路 百草枯 肝损伤 

分 类 号：R575[医药卫生—消化系统]