中国临床药理学杂志2025，Vol.41Issue(17)：2489-2495,7.DOI:10.13699/j.cnki.1001-6821.2025.17.016
益肾祛风方通过调节Nrf2/HO-1介导的铁死亡改善单侧输尿管梗阻大鼠肾纤维化的研究
Research of Yishen Qufeng formulation ameliorates renal fibrosis in unilateral ureteral obstruction rats by regulating Nrf2/HO-1-mediated ferroptosis
摘要
Abstract
Objective To establish a rat model of renal fibrosis induced by unilateral ureteral obstruction(UUO),and investigate the mechanism of the Yishen Qufeng Formula(YQF)improves renal fibrosis through regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)axis to mediate ferroptosis.Methods Eight-week-old SD rats were randomly divided into the sham-operation group,model group,positive control group(dapagliflozin at 20 mg·kg-1·d-1),and experimental-L,-M,-H groups(Yishen Qufeng Formula at 15.21,22.82 and 30.42 g·kg-1·d-1).Except for the sham operation group,rats in the other groups were subjected to left ureteral ligation to establish a renal interstitial fibrosis(RIF)model.After successful modeling,the positive control group and the-L,-M,and-H dose experimental groups were given the corresponding drugs by gavage,while the sham operation group and model group were given an equal volume of 0.9％NaCl by gavage.All rats in the 6 groups were administered once a day for 14 consecutive days.Serum creatinine,urea nitrogen and urine protein levels were detected using a fully automatic integrated biochemical analyzer.The content of transforming growth factor-β1(TGF-β1)was measured by enzyme-linked immunosorbent assay(ELISA).The changes in the relative expression levels of fibrosis-related,oxidative stress-related and ferroptosis-related proteins in renal tissues were determined by Western blotting.Results The levels of serum creatinine in the experimental-M,-H groups,sham operation group,model group and positive control group were(50.24±7.81),(49.15±8.87),(41.96±5.25),(59.44±11.93)and(52.14±8.38)μmol·L-1,respectively;the levels of urea nitrogen were(4.58±0.56),(4.45±0.55),(4.32±0.60),(6.00±1.03)and(6.55±1.02)mmol·L-1 respectively;the levels of urine protein were(640.59±205.70),(538.74±237.98),(526.51±192.62),(982.91±349.13)and(964.26±456.84)mg·d-1,respectively;the relative protein expression levels of glutathione peroxidase 4(GPX4)were 1.62±0.15,3.01±0.41,2.25±0.27,1.01±0.51 and 2.15±0.63,respectively;the relative protein expression levels of cystine/glutamate antiporter(xCT)were 0.62±0.10,1.02±0.06,1.65±0.13,0.52±0.20 and 1.18±0.13,respectively;the relative protein expression levels of Nrf2 were 0.66±0.12,1.04±0.16,1.20±0.10,0.54±0.03 and 1.19±0.14,respectively;the relative protein expression levels of HO-1 were 1.13±0.15,1.21±0.18,2.21±0.17,0.64±0.44 and 1.57±0.26,respectively;the relative protein expression levels of α-smooth muscle actin(α-SMA)were 1.63±0.47,1.13±0.57,0.49±0.91,2.88±0.97 and 1.05±0.60,respectively.There were statistically significant differences in the above indicators between the high-dose experimental group and the model group(all P＜0.05).Conclusion Yishen Qufeng Formula may inhibit ferroptosis by activating the Nrf2/HO-1 signaling pathway,thereby effectively alleviating renal interstitial fibrosis in UUO rats.This provides important theoretical evidence for the mechanism by which the Yishen Qufeng Formula improves renal fibrosis through regulation of ferroptosis.关键词
益肾祛风方/肾纤维化/慢性肾病/铁死亡/单侧输尿管梗阻大鼠Key words
Yishen Qufeng Formula/renal fibrosis/chronic kidney disease/ferroptosis/unilateral ureteral obstruction rats分类
中医学引用本文复制引用
高晶琳,韦缘,周恩超..益肾祛风方通过调节Nrf2/HO-1介导的铁死亡改善单侧输尿管梗阻大鼠肾纤维化的研究[J].中国临床药理学杂志,2025,41(17):2489-2495,7.基金项目
国家自然科学基金面上基金资助项目(82474427) （82474427）
第三批江苏省中医药领军人才基金资助项目(SLJ0319) （SLJ0319）
江苏省研究生实践创新计划基金资助项目(KYCX24-2232) （KYCX24-2232）
江苏省中医院科技基金资助项目(Y2022zj07) （Y2022zj07）
江苏省中医院院级课题面上基金资助项目(Y2202) （Y2202）
