Dapagliflozin can alleviate renal fibrosis in rats with streptozotocin‑induced type 2 diabetes mellitus
- Song Xue
- Ying-Xuan Li
- Xiao-Xiao Lu
- Wei Tang
Affiliations: Department of Endocrinology, Shanghai Changzheng Hospital, Shanghai 200003, P.R. China, Department of Endocrinology, Shanghai Gongli Hospital, Shanghai 200135, P.R. China, Department of Endocrinology, Shanghai Zhoupu Hospital, Shanghai 201318, P.R. China
- Published online on: October 24, 2023 https://doi.org/10.3892/etm.2023.12271
Copyright: © Xue
et al. This is an open access article distributed under the
terms of Creative
Commons Attribution License.
Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
The aim of the present study was to explore the effects of Dapagliflozin on renal fibrosis in streptozotocin (STZ)‑induced type 2 diabetes mellitus (T2DM) rats, and to determine the underlying mechanism of action. A total of 24 SPF male SD rats were randomly divided into 4 groups: A normal (Control) group, model group (STZ‑induced T2DM rats), Dapagliflozin group (STZ‑induced T2DM rats treated with 1 mg/kg Dapagliflozin), and a metformin group (STZ‑induced T2DM rats treated with 200 mg/kg metformin), with 6 rats per a group. Peripheral blood and renal tissues were collected from these rats, and the renal indices of each group were examined. The fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), and serum creatinine (SCr) of rats were detected. After 24 h, the urine was collected and the urine protein levels were measured. Hematoxylin and eosin staining was used to detect histological changes in the rat kidney; Masson staining was used to observe the degree of fibrosis in rat renal tissues; and western blot was performed to determine the expression levels of α‑smooth muscle actin (SMA), vimentin, E‑cadherin, TGF‑β1, Smad7, and p‑Smad3 in rat renal tissues. Dapagliflozin effectively inhibited the increase in FBG and HbA1c levels in diabetic mice, reduced renal tissue damage, reduced the renal index values, reduced collagen deposition in the glomerulus and interstitial area, and reduced the proliferation of glomerular mesangial cells. In addition, Dapagliflozin significantly lowered the levels of BUN, SCr, and 24‑h urine protein, decreased the protein expression of α‑SMA, vimentin, TGF‑β1, and p‑Smad3, and increased the protein expression levels of E‑cadherin and Smad7. Together, these results showed that Dapagliflozin alleviated renal fibrosis in STZ‑induced T2DM rats, and its mechanism of action may be related to the inhibition of the TGF‑β1/Smad pathway.