益肝胶囊对药物性肝损伤大鼠HMGB1、RAGE和NF⁃κB蛋白表达的影响  

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF⁃κB protein in rats with drug⁃induced liver injury

作　　者：唐娅 李君[1] 齐雅芝 曹睿 翟燕玲 韩玉生[1] 徐强[1] TANG Ya;LI Jun;QI Yazhi;CAO Rui;ZHAI Yanling;HAN Yusheng;XU Qiang(Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;Heilongjiang University of Chinese Medicine Jiamusi College,Jiamusi 154007,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学佳木斯学院,黑龙江佳木斯154007

出　　处：《海南医学院学报》2024年第4期248-254,共7页Journal of Hainan Medical University

基　　金：黑龙江省教育厅科研项目(12531608)。

摘　　要：目的:研究益肝胶囊对抗结核药物性肝损伤(ATB‐DILI)中高迁移率族蛋白B1(HMGB1)、核因子‐κB(NF‐κB)和晚期糖基化终末产物受体(RAGE)蛋白表达的影响,探讨其对ATB‐DILI的保护作用和机制,为益肝胶囊的临床应用提供实验依据。方法:将24只大鼠分为两组,除空白组(n=6)灌胃0.9%氯化钠溶液外,其余18只给予异烟肼(INH)+利福平(RFP)(各50 mg⋅kg^(‐1)⋅d^(‐1))连续灌胃4周。然后将18只按每组6只随机分为3组(模型组、益肝胶囊低剂量组、益肝胶囊高剂量组),空白组与模型组继续灌胃0.9%氯化钠溶液,益肝胶囊低剂量组0.468 g/kg,益肝胶囊高剂量组1.872 g/kg[1]进行灌胃给药。4周后,HE染色观察肝的病理变化;检测ALT、AST、ALP、γ‐GT、TBIL的含量;IHC检测HMGB1、NF‐κBp65、RAGE蛋白的表达;WB检测HMGB1、NF‐κBp65、RAGE、TNF‐α和IL‐1β的表达水平。结果:HE染色显示,模型组肝的结构排列较紊乱、肝细胞出现肿胀融合、炎性细胞数量增多并伴有点状坏死,而益肝胶囊各治疗组的上述病理变化有明显的改善;模型组ALT、AST、ALP、γ‐GT、TBIL含量较空白组上升(P<0.05);益肝胶囊各治疗组ALT、AST、ALP、γ‐GT、TBIL含量较模型组显著降低(P<0.05);与空白组比较模型组TNF‐α和IL‐1β的表达水平升高(P<0.05),HMGB1、NF‐κBp65、RAGE的表达增加(P<0.05);与模型组比较益肝胶囊各治疗组TNF‐α和IL‐1β的表达水平降低(P<0.05),HMGB1、NF‐κBp65、RAGE的表达下降(P<0.05)。结论:益肝胶囊可能通过HMGB1/RAGE/NF‐κBp65信号通路,抑制炎性因子的分泌,从而对ATB‐DILI起到保护作用。Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor‐B(NF‐κB)and receptor for advanced glycation end products(RAGE)in anti‐tuberculosis drug‐in‐duced liver injury(ATB‐DILI),and to explore its protective effect and mechanism on ATB‐DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty‐four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg∙kg^(‐1)∙d^(‐1))for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ‐GT and TBIL were detected.The expression of HMGB1,NF‐κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF‐κBp65,RAGE,TNF‐αand IL‐1βwere detected by WB.Results:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ‐GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ‐GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF‐αand IL‐1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF‐κBp65 and RAGE were increased(P<0.05).Compared wit

关 键 词：益肝胶囊 抗结核药物性肝损伤 HMGB1 RAGE NF‐κB 

分 类 号：R285.5[医药卫生—中药学]