Wld ~ S Can Improve Type 1 Diabetes Caused By Kidney Damage

Objectives:The purpose of this study is to investigate whether Wlds (slow Wallerian degeneration; also known as Wld) gene plays a renoprotective role during the progression of DN and the possible mechanisms. It is helpful to further understand the pathogenesis of diabetic nephropathy, and to provide a new idea for the clinical diagnosis and treatment.Methods:(1) Diabetes was induced in eight-week-old male wild-type (WT) and C57BL/Wlds mice by streptozotocin (STZ) injection. Mice were divided into four groups,(DWT;â‘¡WT+STZ;â‘¢Wlds;â‘£Wç”’lds+STZ. Blood and urinary variables including blood glucose, glycated hemoglobin (GHb), insulin, urea nitrogen and albumin/creatinine ratio were assessed4,7and14weeks after STZ injection.(2) Periodic acid-Schiff (PAS) staining, Masson staining and silver staining were performed for renal pathological analyses. In addition, the renal ultrastructure was observed by electron microscope.(3) The activities of p38and ERK signaling in renal cortical tissues were evaluated by western blot. NAD+/NADH ratio and NADPH oxidase activity were also measured. Moreover, the expressions of tumor necrosis factor-a (TNF-a), interleukin-1(IL-1) and IL-6were examined.Results:Our results showed that Wlds improves metabolic disorder in STZ-induced diabetic renal injury model. The kidney weights per body weight, blood urea nitrogen (BUN) and urinary albumin/creatinine ratio kept rising during these14weeks in diabetic WT group, and Wld can significantly inhibit the growth in diabetic group. Wld ameliorated the pathological characteristics including renal hypertrophy, extracellular matrix deposition, thickening of basement membranes and foot process fusion. Additionally, Wlds effectively alleviated the reduction of NAD+/NADH ratio, increased NADPH oxidase activity, upregulated expression of inflammatory cytokines and the activation of p38and ERK signaling pathways in renal tissues of diabetic mice.Conclusions:Wlds improved metabolic disorder and morphology changes in early experimental diabetic renal injury via slowing down the reduction of NAD+/NADH ratio, suppressing enhanced NADPH oxidase activity, inhibiting the up-regulation of inflammatory cytokines and the activation of p38and ERK signaling.