南蛇藤素调节HMGB1/TLR4/NF-κB信号通路对急性肝功能衰竭大鼠炎性损伤的影响  

Effect of celastrol on inflammatory injury in rats with acute liver failure by regulating HMGB1/TLR4/NF-κB signal pathway

作　　者：孙瑞青 邓娟 王秀芳 SUN Ruiqing;DENG Juan;WANG Xiufang(Department of Gastroenterology,Xijing Hospital,Air Force Medical University Xi′an 710032,China)

机构地区：[1]空军军医大学西京医院消化内科,陕西西安710032

出　　处：《胃肠病学和肝病学杂志》2024年第1期28-33,共6页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的 分析南蛇藤素调节HMGB1/TLR4/NF-κB信号通路对急性肝功能衰竭(acute liver failure,ALF)大鼠炎性损伤的影响。方法 将大鼠分为正常组、模型组、南蛇藤素12.5 mg/kg组、南蛇藤素50 mg/kg组、促肝细胞生长素组(2 mg/kg)、南蛇藤素+甘草酸组(50 mg/kg+20 mg/kg),给药干预持续3 d,观察大鼠一般情况,全自动生化分析仪分析大鼠血清肝功能、炎症指标水平,HE染色观测大鼠肝组织病理,TUNEL染色观测大鼠肝细胞凋亡情况,Western blotting法观测大鼠肝组织HMGB1/TLR4/NF-κB通路蛋白表达情况。结果 与正常组相比,模型组大鼠死亡率、血清ALT、AST、TBil水平、肝组织细胞凋亡率、肝组织HMGB1、TLR4、p-NF-κB/NF-κB表达升高(P<0.05);与模型组相比,南蛇藤素12.5 mg/kg组、南蛇藤素50 mg/kg组、促肝细胞生长素组死亡率、血清ALT、AST、TBil水平、肝组织细胞凋亡率、肝组织HMGB1、TLR4、p-NF-κB/NF-κB表达降低(P<0.05);与南蛇藤素50 mg/kg组相比,南蛇藤素+甘草酸组大鼠血清ALT、AST、TBil水平、肝组织细胞凋亡率、肝组织HMGB1、TLR4、p-NF-κB/NF-κB表达降低(P<0.05)。结论 南蛇藤素可能通过抑制HMGB1/TLR4/NF-κB通路降低ALF大鼠肝脏炎症与肝细胞凋亡,保护肝组织。Objective To analyze the effect of celastrol on inflammatory injury in rats with acute liver failure(ALF) by regulating HMGB1/TLR4/NF-κB signal pathway.Methods Rats were divided into normal group,model group,celastrol 12.5 mg/kg group,celastrol 50 mg/kg group,hepatocyte growth promoting factor group(2 mg/kg),celastrol+glycyrrhizic acid group(50 mg/kg+20 mg/kg),the intervention lasted for 3 days.The general condition of rats was observed,the levels of serum liver function and inflammation indexes of rats were analyzed by automatic biochemical analyzer.HE staining was used to observe the pathology of rat liver tissue.TUNEL staining was used to observe the apoptosis of rat hepatocytes,and Western blotting was used to observe the expression of HMGB1/TLR4/NF-κB pathway proteins in rat liver.Results Compared with the normal group,the mortality rate,levels of serum ALT,AST,TBil,apoptosis rate of liver cells,and the expression of HMGB1,TLR4,p-NF-κB/NF-κB in liver tissue of the model group increased(P<0.05).Compared with the model group,the mortality rate,levels of serum ALT,AST,TBil,apoptosis rate of liver cells,and the expression of HMGB1,TLR4,p-NF-κB/NF-κB in liver tissues of the celastrol 12.5 mg/kg and celastrol 50 mg/kg groups and hepatocyte growth promoting factor group decreased(P<0.05).Compared with the celastrol 50 mg/kg group,the levels of serum ALT,AST,TBil,apoptosis rate of liver cells,and the expression of HMGB1,TLR4,p-NF-κB/NF-κB in liver tissues of rats in the celastrol+glycyrrhizic acid group decreased(P<0.05).Conclusion Celastrol may reduce liver inflammation and hepatocyte apoptosis,and protect liver tissue in ALF rats by inhibiting HMGB1/TLR4/NF-κB pathway.

关 键 词：南蛇藤素 急性肝功能衰竭 炎性损伤 HMGB1/TLR4/NF-κB信号通路 

分 类 号：R575[医药卫生—消化系统]