抗纤灵方调控P53/GPX4通路抑制大鼠肾纤维化的机制研究OA

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.