AKT inhibitor delays STZ-induced diabetic nephropathy by blocking EndoMT transformation

Background: Diabetic nephropathy (DN) is one of the most common and serious microvascular complications of diabetes, and a leading cause of end-stage renal disease. Objective: To investigate whether an AKT inhibitor can regulate EndoMT and participate in the pathogenesis of DN. Methods: Thirty Wistar rats were randomly divided into three groups: control, DN model, and AKT inhibitor VIII treatment (20 µM, administered daily via intravenous injection for 4 weeks). Levels of serum creatinine (Scr), blood urea nitrogen (BUN), urinary albumin (UAlb), reactive oxygen species (ROS), superoxide dismutase (SOD), inflammatory factors (IL-6, IL-1?), and the expression of EndoMT-related markers (VE-cadherin, CD31, ?-SMA, collagen I) were measured. Results: Compared with the DN group, the AKT inhibitor significantly decreased the levels of Scr, BUN, UAlb, ROS, IL-6, IL-1?, TGF-?1, ?-SMA, Collagen I and p-AKT (P<0.05), while it increased SOD activity and the expression of VE-Cadherin and CD31. Conclusion: The AKT inhibitor may delay the progression of diabetic nephropathy by inhibiting EndoMT, alleviating inflammation, and reducing oxidative stress.