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2022, Vol. 26 ›› Issue (8): 1216-1222Dapagliflozin improves renal injury in diabetic nephropathy ratsWang Qin1, Shen Cheng2, Liao Jing1, Yang Ye1
Abstract: BACKGROUND: Dapagliflozin has obvious renal protective effect on renal injury caused by diabetic nephropathy. OBJECTIVE: To explore the possible mechanism by which dapagliflozin can improve renal injury in diabetic nephropathy rats through microRNA-126. METHODS: Sprague-Dawley rat models of diabetic nephropathy were successfully established, and randomly divided into a model group, a metformin group and a dapagliflozin group, with six rats in each group. They were given the same dose of normal saline, metformin (500 mg/kg) and dapagliflozin (10 mg/kg) by gavage once a day. Another six rats with normal diet were selected as control group. Twelve weeks later, the rats in each group were killed under anesthesia. Fasting blood glucose, serum creatinine, urea nitrogen and 24-hour urinary microalbumin levels were detected. The level of microRNA-126 in rat kidney was detected by qRT-PCR. The levels of transforming growth factor-β 1, vascular endothelial growth factor receptor 2 and phosphate and tension homology deleted on chromosome ten (PTEN) in rat kidney were detected by qRT-PCR, western blot and immunohistochemistry. The ultrastructural and pathological changes of the rat kidney were observed by electron microscope, hematoxylin-eosin staining and Masson staining. RESULTS AND CONCLUSION: The levels of fasting blood glucose, serum creatinine, urea nitrogen, 24-hour urinary microalbumin, transforming growth factor-β1, and vascular endothelial growth factor receptor 2 in the model group were significantly higher than those in the normal group (P < 0.05), and the levels of microRNA-126 and PTEN were significantly lower than those in the normal group. The levels of fasting blood glucose, serum creatinine, urea nitrogen, 24-hour urinary microalbumin, transforming growth factor-β 1, and vascular endothelial growth factor receptor 2 in the metformin group and dapagliflozin group were significantly lower than those in the model group (P < 0.05), and the levels of microRNA-126 and PTEN were significantly higher than those in the model group. The above changes were more significant in the dapagliflozin group compared with the metformin group (P < 0.05). Renal histopathological findings indicated that compared with the model group, the renal lesions in the metformin group and the dapagliflozin group was milder, the foot process of the dapagliflozin group was better than that of the metformin group, and the renal morphology was relatively normal in the dapagliflozin group. These findings indicate that dapagliflozin can up-regulate the level of microRNA-126, inhibit the expression of transforming growth factor-β 1, and vascular endothelial growth factor receptor 2, promote the expression of PTEN, and delay the process of renal injury in diabetic nephropathy rats. Key words: diabetic nephropathy, dapagliflozin, kidney, microRNA-126, transforming growth factor-β1, vascular endothelial growth factor receptor 2, phosphate and tension homology deleted on chromosome ten |