Intravenous Injection of Nrf2 Plasmid Attenuates Glomerular ROS Injury of Diabetic Mice

Abstract: This study aimed at examining the effects of treatment with streptozotocin (STZ)-induced diabetic mice by intravenous inchina with Nuclear factor erythroid 2-related factor 2 (Nrf2) plasmid via mouse tail vein on diabetic nephropathy (DN) and the potential mechanisms underlying the action of Nrf2. Male CD-1 mice were randomly assigned to four groups: control group (group C); diabetes mellitus group (group DM); diabetes+pcDNA3 plasmid injection group (group DM+V); diabetes+pcDNA3/mNrf2 plasmid injection group (group DM+N). The model of DM was induced by single-dose intraperitoneal injection of streptozocin (STZ). Mice of group DM+V and group DM+N were injected with a shot of pcDNA3 plasmid or pcDNA3/mNrf2 plasmid via mouse tail vein three days after model establishment， respectively. Four weeks later， malondialdehyde (MDA) contents， the expressions of fibronectin (FN)， Nrf2， γ-glutamylcysteine synthethase (γ-GCS) in the glomeruli were detected. We found that Nrf2 could be up-expressed in renal glomeruli by intravenous injection with Nrf2 plasmid; intravenous injection with Nrf2 plasmid significantly reduced the levels of glomerular MDA concentration; mitigated the expression of FN， enhanced Nrf2 nuclear accumulation and target antioxidant gene γ-GCS expression in the glomeruli of diabetic mice. All these results indicated that intravenous injection with Nrf2 plasmid could attenuate the hyperglycaemia-induced glomerular oxidative stress injury and reduce the extracellular matrix (ECM) deposition in diabetic mice. It could be useful for the further gene therapy study of diabetes in vivo.

CSTR: 32200.14.cjcb.2011.07.0004