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
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)