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The Ameliorating Effect of Ononin on Renal Injury in Rats with Type 2 Diabetic Nephropathy via AMPK/SIRT1/FoxO1 Pathway |
YAO Yi, LI Yanli, DING Hongcheng, et al |
Shiyan People's Hospital / Affiliated People's Hospital of Hubei University of Medicine, Hubei Shiyan 442000, China |
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Abstract Objective: To investigate the ameliorating effect of Ononin on renal injury in rats with type 2 diabetic nephropathy via AMPK/SIRT1/FoxO1 pathway.Methods: The DN model of rat was prepared by intraperitoneal injection of streptozotocin. The rats in the low-dose Ononin group and the high-dose Ononin group were given Ononin by gavage (the doses were 50mg/kg and 200mg/kg, respectively), and the positive control group was given metformin (250mg/kg) by gavage, and the negative control group and model group were given the same amount of normal saline by gavage for 16 weeks. The serum levels of BUN, Scr and blood sugar were measured, and pathological examinations of rat kidneys were performed. At the same time, Western Blot method was used to detect the protein levels of SOD, GSH-PX, MDA, AMPK, SIRT1, FoxO1, FN and LC3B in kidney tissue.Results: In the model group, the glomerulus was abnormally enlarged, the mesangial cells proliferated, the mesangial matrix increased, and the interstitial fibrosis. After Ononin and metformin treatment, the glomerular morphology gradually returned to normal, The degree of inflammation and fibrosis transformation in the glomerulus were also improved in varying degrees. Compared with the negative control group, the levels of BUN, Scr, blood sugar, MDA, FoxO1 and FN in the model group, Ononin low-dose group, Ononin high-dose group and positive control group increased, SOD, GSH -PX, AMPK, SIRT1 and LC3B levels decreased(P<0.05). Compared with the model group, the levels of BUN, Scr, blood sugar, MDA, FoxO1 and FN in the low-dose Ononin group, high-dose Ononin group and the positive control group decreased, and SOD, GSH-PX, AMPK, SIRT1 and LC3B increased(P<0.05). Compared with the low-dose Ononin group, the levels of BUN, Scr, blood glucose, MDA, FoxO1 and FN in the high-dose Ononin group and the positive control group decreased, and the levels of SOD, GSH-PX, AMPK, SIRT1 and LC3B increased(P<0.05). There was no significant difference in indexes between the high-dose Ononin group and the positive control group(P>0.05). Conclusion: Ononin has a significant improvement effect on kidney injury in rats with type 2 diabetic nephropathy, and its mechanism may be related to the activation of AMPK/SIRT1/FoxO1 pathway by Ononin.
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