黄芪提取物调节IL-6/STAT3信号通路治疗马兜铃酸Ⅰ诱导肝肾损伤小鼠模型的效果观察  

Efficacy of Astragali Radix extract in treatment of a mouse model of aristolochic acidⅠ-induced liver and renal injury by regulating the IL-6/STAT3 signaling pathway

作　　者：朱哿瑞 皮亚妮 王静[1] 黄恺 彭渊[1] 陈高峰[1] 刘成海[1,3,4] 陶艳艳 ZHU Gerui;PI Yani;WANG Jing;HUANG Kai;PENG Yuan;CHEN Gaofeng;LIU Chenghai;TAO Yanyan(Institute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Institute of TCM International Standardization,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai 201203,China;Key Laboratory of Liver and Kidney Diseases,Ministry of Education,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院·肝病研究所,上海201203 [2]上海中医药大学中医药国际标准化研究所,上海201203 [3]上海市中医临床重点实验室,上海201203 [4]肝肾疾病病证教育部重点实验室(上海中医药大学),上海201203

出　　处：《临床肝胆病杂志》2023年第8期1903-1910,共8页Journal of Clinical Hepatology

基　　金：上海市科委科技支撑项目(19401901500);上海市中医药三年行动计划(ZY-〔2018-2020〕-CCCX-5001)。

摘　　要：目的探讨黄芪提取物(AR)改善马兜铃酸Ⅰ(AAⅠ)致小鼠急性肝、肾损伤效果及其调控IL-6/STAT3信号通路的作用机制。方法健康雄性C57BL/6小鼠38只,采用简单随机分组法分为正常组(n=8)、模型组(n=10)、AR组(n=10)和N-乙酰半胱氨酸(NAC)组(n=10)。模型组小鼠以20 mg/kg AAⅠ腹腔注射,1次/d,持续5 d。正常组小鼠腹腔注射相同容积羧甲基纤维素钠。AR组、NAC组20 mg/kg AAⅠ腹腔注射,1次/d,持续3 d;第4天分别按AR 75 mg/kg、NAC 150 mg/kg小鼠体质量剂量灌胃,1次/d,持续8 d。NAC为阳性对照药。给药造模结束后,处死小鼠并收集血清及肝、肾组织。试剂盒检测血清ALT、AST、肌酐(SCr)、尿素氮(BUN)水平;HE染色观察肝、肾组织病理;荧光PCR及免疫组化分析肝、肾组织中p-STAT3表达量;酶联免疫吸附实验检测肝、肾组织IL-6、IL-1β及TNF-α表达水平。计量资料多组间比较采用单因素方差分析,进一步两组间比较采用SNK-q检验。结果与正常组小鼠相比,模型组小鼠肾体比上升(P<0.05);与模型组相比,AR组ALT、AST、SCr和BUN水平显著降低(F值分别为49.29、31.31、58.89、85.88,P值均<0.01);HE染色结果表明,AR可有效减轻AAⅠ导致的肝、肾组织结构破坏和炎性细胞浸润;荧光PCR及免疫组化染色结果表明,AR可减少肝、肾组织p-STAT3表达;酶联免疫吸附检测发现,AR可下调IL-6、IL-1β及TNF-α表达。NAC与AR效应相似,两者间无明显差异。结论AR对AAⅠ所致急性肝、肾损伤有保护作用,其部分作用机制可能与抑制IL-6/STAT3信号通路激活,减轻炎症反应有关。Objective To investigate the mechanism of action of Astragali Radix(AR)extract in improving aristolochic acidⅠ(AAⅠ)-induced acute liver and renal injury in mice by regulating the IL-6/STAT3 signaling pathway.Methods A total of 38 healthy male C57BL/6 mice were randomly divided into normal group with 8 mice,model group with 10 mice,AR group with 10 mice,and N-Acetyl-L-cysteine(NAC)group with 10 mice.The model group mice were intraperitoneally injected with 20 mg/kg AAⅠonce a day for 5 days.Normal mice were intraperitoneally injected with the same volume of Carboxymethyl cellulose sodium.AR group and NAC group received intraperitoneal injection of 20 mg/kg AAⅠonce a day for 3 days;On the 4th day,mice were gavaged with AR 75 mg/kg and NAC 150 mg/kg body mass doses,once a day,for 8 days.NAC was used as a positive control drug.After the end of administration and modeling,the mice were sacrificed to collect serum samples and liver and renal tissue samples.The kit was used to measure the serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum creatinine(SCr),and blood urea nitrogen(BUN);HE staining was used to observe liver and renal histopathology;quantitative real-time PCR and immunohistochemistry were used to measure the expression level of p-STAT3 in the liver and renal tissue;ELISA was used to measure the expression levels of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in the liver and renal tissue.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the SNK-q test was used for further comparison between two groups.Results Compared with the normal group,the model group had a significant increase in kidney-to-body ratio(P<0.05).Compared with the model group,the AR group had significant reductions in the levels of ALT,AST,SCr,and BUN(F=49.29,31.31,58.89,and 85.88,all P<0.01).HE staining showed that AR could effectively alleviate AAⅠ-induced structural damage and inflammatory cell infiltration in

关 键 词：马兜铃酸 化学性与药物性肝损伤 急性肾损伤 STAT3转录因子 黄芪 

分 类 号：R285.5[医药卫生—中药学]