Objective To investigate whether the VEGF-A inhibitor sFLT-1 can reverse the renal damage in type 1 diabetic mice by inhibiting the activation and inflammatory response of vascular endothelial cells.
Methods Eight-week-old C57BL/6 female mice were divided into 5 weeks: healthy control group (n = 5), diabetic group (n = 5) and 15 weeks: healthy control group (n = 5), diabetic group (n = 5), the control + sFLT-1 treatment group (n = 5), the diabetes + sFLT-1 treatment group (n = 5), the type 1 diabetes model was established by intraperitoneal injection of streptozotocin (75 mg/kg). Treatment with sFLT-1 started at 6 weeks after modeling. The renal tissue pathological damage, the degree of macrophage infiltration, the degree of activation of glomerular endothelial cells and the level of inflammation were observed before and after sFLT-1 treatment.
Results Compared with the model group, transfection of sFLT-1 could significantly reduce the content of glomerular mesangial matrix (namely the level of glomerular type IV collagen) (P<0.001), and the infiltration of glomerular macrophages (P<0.001). < 0. 001), glomerular endothelial cell activation (P < 0. 001), and glomerular tumor necrosis factor-α levels (P < 0. 001), thereby significantly inhibiting diabetic kidney injury, and sFLT-1 in vitro Can reduce endothelial cell activation induced by vascular endothelial growth factor-A (P<0.001).
Conclusions sFLT-1 may reduce endothelial activation and glomerular inflammation by inhibiting VEGF-A, and ultimately reverse diabetes-related renal damage. It is a new therapeutic direction for diabetic nephropathy.