黄芪甲苷调控HMGB1/NF-κB通路对脓毒症大鼠巨噬细胞极化和急性肾损伤的机制研究  

Mechanism of astragaloside regulating HMGB1/NF-κB pathway on macrophage polarization and acute kidney injury in sepsis rats

作　　者：吕冬菊 黄东明 段伟静 LV Dongju;HUANG Dongming;DUAN Wejing(Department of Pharmacy,People's Hospital Afiliated to Shandong First Medical University,Jinan 271199;Department of Dermatology,Jinan Hospital of Integrated Chinese and Westem Medicine,Jinan 271199,China)

机构地区：[1]山东第一医科大学附属人民医院药剂科,山东省济南市271199 [2]济南市中西医结合医院皮肤科,山东省济南市271199

出　　处：《中国煤炭工业医学杂志》2025年第1期1-7,共7页Chinese Journal of Coal Industry Medicine

基　　金：山东省优秀中青年科学家科研奖励基金(编号:BS2020SW1008)。

摘　　要：目的 探究黄芪甲苷能否调控高迁移率族蛋白B1/转录因子κB(HMGB1/NF-κB)信号通路影响脓毒症大鼠巨噬细胞极化和急性肾损伤。方法 将40只大鼠随机分为对照组(Control组)、模型组(sepsis组)、黄芪甲苷组(AS-Ⅳ组)和黄芪甲苷+NF-κB mimics组(AS-Ⅳ+NF-κB组),每组10只。采用酶联免疫吸附试验(ELISA)检测各组大鼠肾功能指标血尿素氮(BUN)、肌酐(Scr)水平和炎症因子中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、白介素1β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平;采用苏木精-伊红(HE)染色和过碘酸雪夫(PAS)染色观察大鼠肾组织病理学变化;采用免疫荧光染色法检测肾组织中F4/80、诱导型一氧化氮合酶(iNOS)、精氨酸酶(Arg-1)阳性表达;采用蛋白质印迹法检测肾组织中i NOS、Arg-1、HMGB1、NF-κB p65蛋白表达。结果 与Control组比较,sepsis组大鼠血清中BUN、Scr、NGAL、IL-1β、IL-6、TNF-α含量、肾组织中F4/80与iNOS共染色阳性表达及肾组织中i NOS、HMGB1、NF-κB p65蛋白表达均明显升高(P<0.05),肾组织中F4/80与Arg-1共染色阳性表达及Arg-1蛋白表达明显减少(P<0.05);与sepsis组比较,AS-Ⅳ组大鼠血清中BUN、Scr、NGAL、IL-1β、IL-6、TNF-α含量、肾组织中F4/80与i NOS共染色阳性表达及肾组织中i NOS、HMGB1、NF-κB p65蛋白表达均明显降低(P<0.05),肾组织中F4/80与Arg-1共染色阳性表达及Arg-1蛋白表达明显减少(P<0.05);与AS-Ⅳ组比较,AS-Ⅳ+NF-κB组大鼠血清中BUN、Scr、NGAL、IL-1β、IL-6、TNF-α含量、肾组织中F4/80与iNOS共染色阳性表达及肾组织中i NOS、HMGB1、NF-κB p65蛋白表达均明显升高(P<0.05),肾组织中F4/80与Arg-1共染色阳性表达及Arg-1蛋白表达明显减少(P<0.05)。结论 黄芪甲苷可抑制脓毒症大鼠急性肾损伤,促进巨噬细胞M2型极化,其作用机制可能和抑制HMGB1/NF-κB信号通路有关。Objective To investigate whether Astragaloside IV can regulate the high mobility group protein B1/transcription factor kappa B(HMGB1/NF-κB)signaling pathway and affect macrophage polarization and acute kidney injury in septic rats.Methods Forty rats were randomly divided into a control group(Control group),a model group(Sepsis group),an Astragaloside IV group(AS-IV group),and an Astragaloside IV+NF-κB mimics group(AS-IV+NF-κB group),with 10 rats in each group.Enzyme linked immunosorbent assay(ELISA)was used to detect renal function indicators such as blood urea nitrogen(BUN),creatinine(Scr)levels,and inflammatory factor indicators such as neutrophil gelatinase associated lipocalin(NGAL),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor alpha(TNF-α)levels in each group of rats.Hematoxylin eosin(HE)staining and PAS staining were used to detect pathological changes in rat kidney tissue.Immunofluorescence staining was used to detect the positive expression of F4/80,inducible nitric oxide synthase(iNOS),and arginase(Arg-1)in renal tissue.Western blot was used to detect the expression of iNOS,Arg-1,HMGB1,and NF-κB p65 proteins in renal tissue.Results Compared with Control group,the serum levels of BUN,Scr,NGAL,IL-1β,IL-6 and TNF-α,the positive expression of F4/80 co-staining with iNOS and the protein expression of iNOS,HMGB1,and NFκB p65 in renal tssues were significantly higher in sepsis group(P<0.05),and the positive expression of F4/80 co-staining with Arg-1 and the protein expression of Arg-1 were significantly lower(P<0.05).Compared with the sepsis group,serum levels of BUN,Scr,NGAL,IL-1β,IL-6 and TNF-α,positive expression of F4/80 and iNOS co-staining in renal tissues and iNOS,HMGB1,and NF-κB p65 protein expression in renal tisues were allsignificantly reduced in the AS-IV group rats(P<0.05).Compared with AS-IV group,the serum levels of BUN,Scr,NGAL,IL-1β,IL-6,TNF-α,the positive expression of F4/80 co-staining with iNOS and the positive expression of iNOS,HMGB1,and NF-κB p65 in r

关 键 词：黄芪甲苷 巨噬细胞极化 脓毒症 急性肾损伤 HMGB1/NF-κB信号通路 

分 类 号：R552[医药卫生—血液循环系统疾病]