Hyperoside regulates Nrf2/HO-1/NQO1 signaling pathway to alleviate renal ischemia-reperfusion injury in rats
AIM To explore the regulation effect of hyperoside on renal ischemia-reperfusion(IR)injury and nuclear factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1)/quinone oxidoreductase 1(NQO1)signaling pathway in rats.METHODS The models of renal IR rat were constructed by ligating bilateral renal arteries(60 minutes)and recovering perfusion(120 minutes).Forty SD rats were randomly divided into control group,model group and hyperoside 12.5,25,50 mg·kg-1 groups.The samples of blood and renal tissues were collected to detect levels of 24 h proteinuria,serum creatinine,blood urea nitrogen and superoxide dismutase(SOD),malondialdehyde(MDA).The renal tissue lesions were observed by HE staining.The expression of caspase-3 was detected by immunohistochemistry.The expression of inducible nitric oxide synthase(iNOS),interleukin(IL)-6 and IL-10 mRNA was detected by qRT-PCR.The expression of Bcl-2,Bax,Nrf2,HO-1 and NQO1 proteins in renal tissues was detected by Western blot.A total of 32 rats were randomly and averagely divided into control group,model group,hyperoside(50 mg·kg-1)group and hyperoside+ML385(30 mg· kg-1)group for relevant detection.RESULTS Compared with the model group,the levels of 24 h proteinuria,serum creatinine and blood urea nitrogen,and MDA were significantly decreased,while the levels of SOD were significantly increased in the hyperoside 25 and 50 mg·kg-1 groups(P＜0.05).HE staining showed that there was obvious pathological injury of renal tissues and inflammatory cells infiltration was severe in the model group.The pathological injury were relieved in the hyperoside groups,and the improvement were more significant in the hyperoside 50 mg·kg-1 group.Compared with the model group,the expression of Bax/Bcl-2,caspase-3,iNOS and IL-6 mRNA were decreased significantly,while the expression of IL-10 mRNA,p-Nrf2/Nrf2,HO-1 and NQO1 and SOD were significantly upregulated in the hyperoside 25 and 50 mg·kg-1 groups(P＜0.05).The expression of Bax/Bcl-2 decreased significantly in the hyperoside 12.5 mg·kg-1 group(P＜0.05).ML385 can partially block the improvement effect of hyperoside on renal IR rats.CONCLUSION Hyperoside may inhibit apoptosis of renal cells,excessive oxidative stress and inflammatory response by up-regulating Nrf2/HO-1/NQO1 signaling pathways,and relieve renal IR injury.
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