文献类型：期刊文献

中文题名：瘀方通过抑制铁死亡介导的肾小管损伤与炎症反应减轻UUO诱导的肾纤维化

英文题名：Amelioration of UUO-Induced Renal Fibrosis by"Yu Fang"via Suppression of Ferroptosis-Mediated Tubular Injury and Inflammation

作者：梁丽娟[1,2,3];米友军[4];罗慧英[5];党冰融[6];黄昀雅[1];戴恩来[1]

第一作者：梁丽娟

机构：[1]甘肃中医药大学中西医结合学院;[2]甘肃中医药大学第一临床医学院;[3]敦煌医学与转化教育部重点实验室;[4]兰州大学基础医学院;[5]甘肃中医药大学药学院,甘肃兰州730100;[6]榆中县中医院检验科,甘肃兰州730199

第一机构：甘肃中医药大学中西医结合学院

年份：2026

卷号：42

期号：3

起止页码：566

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(No 8216140859);甘肃省高等学校创新基金项目(No 2022B-118);敦煌医学与转化教育部重点实验室(No DHXY20-08)。

语种：中文

中文关键词：肾纤维化;单侧输尿管梗阻;铁死亡;武威汉简“瘀方”;肾小管上皮细胞

外文关键词：renal fibrosis;unilateral ureteral obstruction(UUO);ferroptosis;Wuwei Han Bamboo Slips“Yu Fang”;Tubular Epithelial Cells

摘要：目的探讨铁死亡在单侧输尿管结扎(unilateral ureteral obstruction,UUO)诱导的肾纤维化中的作用,并阐明中药复方“瘀方”通过GPX4轴发挥抗纤维化作用的机制。方法建立UUO大鼠模型,分为假手术组、UUO组、UUO+瘀方组和UUO+Fer-1组。通过病理学及生化检测评估肾脏形态、功能及纤维化程度,并采用免疫组化、Western blot及ELISA检测GPX4、脂质过氧化及谷胱甘肽(GSH)水平等铁死亡相关指标。结果UUO组出现明显的肾小管损伤、功能下降及胶原沉积,并伴有GPX4表达下调、脂质过氧化增强及羟脯氨酸含量升高等铁死亡特征。瘀方及Fer-1干预均明显改善肾组织病理损伤,恢复肾功能,减少胶原沉积。机制上,瘀方可激活GSH-GPX4抗氧化轴,降低脂质过氧化水平,抑制铁死亡;同时减弱促纤维化因子表达及肌成纤维细胞活化,从而延缓肾间质纤维化进程。结论铁死亡在UUO诱导的肾纤维化中发挥重要作用。瘀方可通过调控GSH-GPX4轴抑制铁死亡和氧化应激,减轻纤维化进展。
Aim To investigate the role of ferroptosis in renal fibrosis induced by unilateral ureteral obstruction(UUO)and to elucidate the antifibrotic mechanism of the traditional Chinese medicine formula Yu Fang through the GPX4 axis.Methods A UUO rat model was established and divided into four groups:sham-operated,UUO,UUO+Yu Fang,and UUO+ferrostatin-1(Fer-1).Renal morphology,function,and fibrosis were evaluated using histopathology and biochemical assays.Ferroptosis-related indicators,including GPX4 expression,lipid peroxidation,and glutathione(GSH)levels,were assessed using immunohistochemistry,Western blot,and ELISA.Results The UUO group exhibited marked tubular injury,renal dysfunction,and collagen deposition.Renal tissues showed characteristic features of ferroptosis,such as decreased GPX4 expression,elevated lipid peroxidation,and excessive hydroxyproline accumulation.Both Yu Fang and Fer-1 treatment significantly alleviated tubular damage,restored renal function,and reduced collagen deposition.Mechanistically,Yu Fang enhanced the GSH-GPX4 antioxidant axis,reduced lipid peroxidation,and inhibited ferroptosis.Furthermore,Yu Fang suppressed the expression of profibrotic factors and inhibited myofibroblast activation,thereby attenuating renal interstitial fibrosis.Conclu-sions Ferroptosis plays a critical role in UUOinduced renal fibrosis.Yu Fang mitigates ferroptosis and fibrosis progression by modulating the GSH-GPX4 axis,reducing oxidative stress and myofibroblast activation.These findings provide experimental evidence supporting Yu Fang as a promising therapeutic strategy for renal fibrosis targeting ferroptosis.