MiR-20a ameliorates diabetic angiopathy in streptozotocin-induced diabetic rats by regulating intracellular antioxidant enzymes and VEGF.

Abstract

We evaluated the beneficial effect of miR-20a mimic against diabetic angiopathy (DA) in rats by regulating intracellular antioxidant enzymes and vascular endothelial growth factor (VEGF). Diabetes was induced by intraperitoneal administration of streptozotocin (STZ; 65 mg/kg). Rats were then treated with miR-20a mimic (250 nmol/kg orally) for 8 weeks after STZ administration. The effect of miR-20a mimic against DA in rats was evaluated by estimating serum glucose concentration, lipid profile, Lp-a, kidney function test, inflammatory mediators, and markers of endothelial cell function. Markers of oxidative stress in the aortic tissue were estimated in rats treated with miR-20a mimic. Western blot assay, RT-PCR, and histopathology of kidney and myocardial tissues were also performed. Serum levels of blood glucose and markers of renal function were significantly lower, and the lipid profile improved in the miR-20a mimic group compared to the DA group. Treatment with miR-20a mimic ameliorated the altered markers of endothelial function and oxidative stress, as well as mediators of inflammation, in the DA rats. Protein expressions of ERK1/2, JNK, and p38 MAPK, as well as mRNA expressions of TLR-4 and NF-κB, in aortic tissues were lower in the miR-20a mimic group than in the DA group. The miR-20a mimic group had fewer histopathological changes in kidney and myocardial tissues than the DA group. MiR-20a mimic can protect against DA in rats by regulating vascular endothelial function and oxidative stress.