Wusangyin regulates SIRT1-Nrf2 pathway to attenuate renal injury and fibrosis in diabetic mice
AIM:To explore the mechanism of Wusangyin in alleviating renal injury induced by diabetes in mice.METHODS:A diabetic model was established through intraperitoneal injection of streptozotocin following a high-fat and high-sugar diet in mice.The mice were randomly divided into a diabetes model group,a Wusangyin treatment group,and a normal control group.Various assays,including biochemical analyses,HE,PAS,and Masson staining,were employed to assess the impact of Wusangyin on renal function,histomorphology,fibrosis,and related parameters in diabetic nephropathy mice.TUNEL staining was utilized to analyze apoptosis in mouse kidney tissue,and DHE staining was employed to assess intracellular reactive oxygen species levels in kidney tissue cells.Colorimetric analysis of oxidative stress indicators in renal tissue,including lipid peroxidation product malondialdehyde(MDA),antioxidant enzyme super-oxide dismutase(SOD),and catalase(CAT).RT-qPCR was used to detect the mRNA expression of α-smooth muscle ac-tin(α-SMA),collagen Ⅰ,collagen Ⅲ,Bax and Bcl-2.Western blot was used to analyze the expression of silent informa-tion regulator 1(SIRT1)and nuclear factor E2-related factor 2(Nrf2)proteins in renal tissue.RESULTS:After 8 weeks of administration of Wusangyin,compared with control group,the mice in model group showed significant increases in kid-ney hypertrophy index,fasting blood glucose,glycated hemoglobin,triglyceride,total cholesterol,serum creatinine,and blood urea nitrogen(P<0.05).These indicators of the mice in Wusangyin group were significantly lower than those in model group(P<0.05).The 24-hour urinary albumin excretion rate and 24-hour urinary total protein of the mice in Wu-sangyin group were also markedly higher than those in model group.The HE,PAS,and Masson staining of mouse kidney tissues showed that glomerular hypertrophy,basement membrane thickening and renal fibrosis occurred in model group.At the same time,all kinds of lesions in Wusangyin group were significantly alleviated,and renal fibrosis-related mole-cules,α-SMA,collagen Ⅰ and collagen Ⅲ,were significantly reduced compared with model group(P<0.05).Further-more,the Wusangyin group exhibited reduced apoptosis,intracellular reactive oxygen species,and MDA content of renal tissue lipid peroxidation products,along with increased activity of antioxidant enzymes(SOD and CAT).The protein ex-pression levels of SIRT1 and Nrf2 were significantly elevated in the kidney tissue of Wusangyin-treated mice compared with model group(P<0.05).CONCLUSION:Wusangyin can potentially enhance renal function and attenuate renal pathological damage,fibrosis,cell apoptosis and oxidative stress in diabetic nephropathy mice.The observed renal protec-tive effects may be attributed to increased expression of SIRT1 and Nrf2 proteins.
diabetic nephropathyrenal fibrosisWusangyinsilent information regulator 1nuclear factor E2-related factor 2
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NSTL
万方数据
维普
