THE EFFECT AND MECHANISM OF DAPAGLIFLOZIN ON RENAL FIBROSIS IN RATS WITH DIABETIC NEPHROPATHY

Objective: To investigate the effect of dapagliflozin on renal fibrosis among rats with diabetic nephropathy and to analyse its target and molecular mechanism. Methods: Sixty rats were randomly divided into treatment and control groups (n=30 rats per group). Each day for 12 weeks, the control group was injected with normal saline, while the treatment group was injected with 3 mg/ kg dapagliflozin. After 12 weeks, the rats' kidneys were removed and kidney weight/body weight ratios were compared among groups. Urine protein concentration, urine creatine (UCR), blood urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH Px) were measured during this time as well. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect concentrations of collagen IV, fibronectin, E-cadherin, alpha-smooth muscle actin (alpha-SMA), N-cadherin, Smad2, Smad3, phosphorylated smad2 (p-smad2), p-smad3, and transforming growth factor-beta 1 (TGF-beta 1). Results: Dapagliflozin can significantly reduce renal fibrosis in rats with diabetic nephropathy. Conclusion: This animal modelling study in rats with diabetic nephropathy provides important clinical data and evidence supporting the use of dapagliflozin as an effective drug for the treatment of nephropathy and renal fibrosis.