时珍国医国药2026，Vol.37Issue(18)：3474-3481,8.DOI:10.70976/j.1008-0805.SZGYGY-2026-1810
大黄甘草汤调控SIRT3/HIF-1α/hepcidin轴抑制肾间质纤维化的作用机制研究
Study on the mechanism of Dahuang Gancao Decoction(大黄甘草汤)inhibits renal interstitial fibrosis by regulating the SIRT3/HIF-1α/hepcidin axis
摘要
Abstract
Objective To investigate the potential effects and mechanisms of Dahuang Gancao Decoction(大黄甘草汤,DHGCD)on adenine-diet-induced renal interstitial fibrosis(RIF)in mice.Methods A mouse model of RIF was induced by an adenine diet and treated with DHGCD.Renal function was assessed by measuring blood urea nitrogen(BUN)and serum creatinine(Scr)levels.Masson's trichrome staining was used to evaluate renal collagen deposition.The primary sites of iron homeostasis imbalance in the kid-neys were determined by assessing the co-localization of hepcidin and related proteins.Protein levels of SIRT3,HIF-1α,and hepcidin were detected by Western blot(WB).Subsequently,renal function,fibrosis,and iron homeostasis were evaluated in SIRT3-knockout mice to validate the hypothesis.Results In the adenine-diet-induced renal injury mouse model,the primary binding site of hepcidin in the kidneys was localized for the first time to the renal tubular collecting duct.DHGCD intervention significantly attenuated the progres-sion of renal dysfunction and markedly inhibited collagen deposition in renal tissues,indicating anti-renal fibrotic effects.Further mechanistic studies revealed that DHGCD activated SIRT3 expression,reduced the acetylation level of HIF-1α,and suppressed the activation of the hepcidin signaling pathway in the kidneys.However,in SIRT3 knockout mice,DHGCD failed to significantly amelio-rate renal fibrosis or iron metabolism disorders,suggesting that its renal protective effects are dependent on SIRT3 activation.Conclu-sion SIRT3 is a key target regulated by DHGCD.The ability of DHGCD to modulate the SIRT3/HIF-1α signaling pathway may repre-sent a feasible therapeutic approach for RIF.关键词
大黄甘草汤/CKD/肾纤维化/SIRT3/铁调素/HIF-1αKey words
Dahuang Gancao Decoction(大黄甘草汤)/Chronic kidney disease/Renal fibrosis/SIRT3/Hepcidin/HIF-1α分类
医药卫生引用本文复制引用
李成银,巴元明,熊致立,王瑞,安熠,关冰,赵井苓..大黄甘草汤调控SIRT3/HIF-1α/hepcidin轴抑制肾间质纤维化的作用机制研究[J].时珍国医国药,2026,37(18):3474-3481,8.基金项目
国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号) （国中医药人教函[2022]75号）
湖北省自然科学基金重点项目(2022CFD023) （2022CFD023）
国家中医药管理局第六批全国中医临床优秀人才研修项目(国中医药人教函〔2025〕256号) （国中医药人教函〔2025〕256号）
湖北中医药大学2025年校级研究生工作站建设点项目华沃生物科技(武汉)有限公司工作站(中医研[2025]50号) （武汉）
湖北省自然科学基金重点项目(2024AFD316) （2024AFD316）
武汉市卫生健康委员会武汉市中医药科研项目面上项目(WZ22B01) （WZ22B01）
湖北中医药大学2022年度中医药传承创新计划/思政专项资助项目(2022SZXC005) （2022SZXC005）
武汉市卫健委2023年中医药科研项目(S202406080021) （S202406080021）
全省重大疑难疾病中西医临床协作项目(鄂卫通[2023]52号) （鄂卫通[2023]52号）
