Effect of Soufeng Jiedu Decoction on Renal Oxidative Stress and Autophagy in Mice with Cisplatin-induced Acute Kidney In-jury
[Objective]To investigate the effect and mechanism of Soufeng Jiedu Decoction on cisplatin-induced acute kidney injury.[Methods]Forty C57BL/6J mice were randomly divided into 5 groups,8 mice in each group:control group and model group were gavaged with distilled water,positive control group was gavaged with prednisolone 5 mg/(kg·d),Soufeng Jiedu Decoction low and high dose groups were gavaged with Soufeng Jiedu Decoction 300 and 500 mg/(kg·d)respectively.These drugs were administered continuously for 10 days.On the 7th day of administration,mice in model group,positive control group,Soufeng Jiedu Decoction low dose group,and Soufeng Jiedu Decoction high dose group were intraperitoneally injected with 20 mg·kg-1 cisplatin,while the control group received an equivalent volume of 0.9%sodium chloride solution.Biochemical approaches were utilized to measure the levels of blood urea nitrogen(BUN),serum creatinine(SCr),malondialdehyde(MDA),and the activity of superoxide dismutase(SOD)and catalase(CAT).Kidney tissue pathological morphology was assessed using hematoxylin-eosin(HE)staining in all groups.Real time-quantitative polymerase chain reaction(RT-qPCR)was employed to determine the gene expressions of kidney injury molecule-1(Kim-1),neutrophil gelatinase-associated lipocalin(Ngal),quinone oxidoreductase 1(Nqo1)and glutamate cysteine ligase(Gclm)in the kidney of mice.Western blot analysis was conducted to evaluate the protein expressions of nuclear factor erythroid 2-related factor 2(NRF2),heme oxygenase-1(HO-1),p62,microtubule-associated protein light chain 3(LC3B)and phosphorylated-AMP-activated protein kinase(p-AMPK).[Results]Compared with control group,model group exhibited a significant increase in levels of BUN and SCr,as well as upregulation of Kim-1 and Ngal gene expression(P<0.01).Notably,severe kidney injury was observed in model group,characterized by tubular degeneration,edema,necrosis,cystic dilatation with focal hemorrhage.Moreover,model group exhibited a significant increase in MDA levels,accompanied by a notable decrease in CAT and SOD activities(P<0.01).On the other hand,model group displayed elevated expressions of renal Nqo1 and Gclm genes,as well as increased protein expressions of NRF2,HO-1,and LC3B,while the protein expressions of p62 and p-AMPK were significantly reduced(P<0.01).Compared with model group,treatment with Soufeng Jiedu Decoction resulted in a significant reduction in BUN and SCr levels,as well as suppression of Kim-1 and Ngal gene expression in the kidney of mice.Furthermore,Soufeng Jiedu Decoction ameliorated acute kidney injury-associated renal tissue lesions.Treatment with Soufeng Jiedu Decoction also led to a decrease in MDA levels,and an increase in CAT and SOD activities within the kidney.Additionally,Soufeng Jiedu Decoction promoted the expression of Nqo1 and Gclm genes,as well as the protein expressions of NRF2,HO-1,LC3B and p-AMPK,while inhibiting the expression of p62 protein(P<0.01).[Conclusion]Soufeng Jiedu Decoction effectively alleviates cisplatin-induced acute kidney injury possibly by inhibiting oxidative stress and promoting autophagy in the kidney.
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