Therapeutic effects of CTLA-4-Ig on diabetic nephropathy in type 2 diabetes mellitus rats ascribed to protection of CTLA-4-Ig on podocytes

Aim: The aim of this study was to investigate the therapeutic effects of CTLA-4-Ig on diabetic nephropathy (DN) and potential mechanism in rats with type 2 diabetes mellitus (T2DM). Methods: Rats were randomly divided into the control group, the T2DM group and the CTLA-4-Ig group. In the CTLA-4-Ig group, rats were treated with CTLA4-Ig for 8 weeks. Results: Fasting blood glucose, endogenous creatinine clearance, 24-h urinary albumin excretion rate, and glomerular hypertrophy index (GHI) in the T2DM and CTLA-4-Ig groups were significantly higher than in the control group (P<0.05). Endogenous creatinine clearance, 24-h urinary albumin excretion rate, and GHI in the CTLA4-Ig group were significantly lower than in the T2DM group (P<0.05). Renal arterial peak blood flow velocities in the systolic and end-diastolic phases, and mean blood flow velocity were the lowest in T2DM group and highest in the control group, and significant differences were observed among three groups (P<0.05). The renal arterial accelerated velocity, pulsatility index, and resistance index in the systolic phase were highest in the T2DM group and lowest in the control group (P<0.05). Expression of podocin and nephrin was highest in the control group and lowest in the T2DM group, and significant difference was observed among three groups (P<0.05). Renal parenchymal structure and podocyte ultrastructure were significantly altered in the DN group and the CTLA-4-Ig group, and the pathological changes in DN group were more severe than in the CTLA-4-Ig group. Conclusion: Therapeutic effects of CTLA-4-Ig on DN are ascribed to the protection of CTLA-4-Ig on podocytes, but not related to the glomerular endothelial cells.