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抗纤灵方调控P53/GPX4通路抑制大鼠肾纤维化的机制研究

姚卫国 余海洋 余双 严湘磊 刘琨 吉晶

时珍国医国药2026,Vol.37Issue(3):410-416,7.
时珍国医国药2026,Vol.37Issue(3):410-416,7.DOI:10.70976/j.1008-0805.SZGYGY-2026-0302

抗纤灵方调控P53/GPX4通路抑制大鼠肾纤维化的机制研究

Mechanism research of Kangxianling Formula(抗纤灵方)in regulating P53/GPX4 pathway to inhibit renal fibrosis in rats

姚卫国 1余海洋 2余双 3严湘磊 1刘琨 1吉晶2

作者信息

  • 1. 上海市第六人民医院金山分院,上海 201500
  • 2. 上海中医药大学附属市中医医院,上海 200040
  • 3. 海军军医大学第三附属医院,上海 201805
  • 折叠

摘要

Abstract

Objective To explore the mechanism of Kangxianling Formula(抗纤灵方,KXLF)in improving renal fibrosis.Methods Experimental rats were divided into Sham operation group,model group,Losartan potassium group,low-dose KXLF group and high-dose KXLF group.Except for the Sham operation group,the other groups established renal fibrosis models by 5/6 nephrectomy.After 12 weeks,serum creatinine(Scr),blood urea nitrogen(BUN),24h urinary protein(24h-Pro),malondialdehyde(MDA),superoxide dis-mutase(T-SOD)activity and Fe2+concentration in kidney were detected.Hematoxylin-eosin(HE)staining assessed renal pathological changes.Immunohistochemistry(IHC)detected the positive expression of Fibronectin(Fn)and α-smooth muscle actin(α-SMA)in renal tissues,while Western blot(WB)and RT-qPCR measured the expression levels of P53,GPX4,and the member 11 of Solute Car-rier Family 7(SLC7A11)in renal tissues.Results Compared with the Sham group,the model group showed significantly decreased levels of T-SOD activity,the levels of Scr,BUN,24h-Pro,MDA,concentration of Fe2+in renal tissue,Fn,α-SMA protein,P53 pro-tein and mRNA(P<0.01).GPX4,SLC7A11 protein and mRNA expression levels in renal tissue were decreased significantly(P<0.01).Renal tubule dilatation,glomerulosclerosis,collagen deposition and interstitial inflammatory cell infiltration were obvious.KXLF intervention reversed these indexes to varying degrees,and renal tissue damage was significantly alleviated,especially in the high-dose group(P<0.01).Conclusion KXLF could improve renal interstitial fibrosis in 5/6 nephrectomy rats,which may be related to modulating P53/GPX4 pathway and inhibiting ferroptosis.

关键词

抗纤灵方/肾纤维化/铁死亡/5/6肾切除/P53/GPX4通路

Key words

Kangxianling Formula(抗纤灵方)/Renal fibrosis/Ferroptosis/5/6 nephrectomy/P53/GPX4 signaling pathway

分类

医药卫生

引用本文复制引用

姚卫国,余海洋,余双,严湘磊,刘琨,吉晶..抗纤灵方调控P53/GPX4通路抑制大鼠肾纤维化的机制研究[J].时珍国医国药,2026,37(3):410-416,7.

基金项目

国家自然科学基金(82405251) (82405251)

上海市名老中医学术经验研究工作室建设项目(SHGZS-202237) (SHGZS-202237)

上海市"十四五"中医药特色专业建设项目(ZYTSZK2-13) (ZYTSZK2-13)

时珍国医国药

1008-0805

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