熊果酸调控VEGF/COX-2/MMP-2通路减轻糖尿病小鼠视网膜病变损伤OA

Aim To investigate the beneficial effects of ursolic acid(UA)to alleviate retinal injury in diabetic mice through the mechanism of regulating vascular endothelial growth factor(VEGF)/cyclooxygenase-2(COX-2)/matrix metalloproteinase-2(MMP-2)pathway.Methods A diabetic retinopathy(DR)mouse model was established and divided into four groups.The UA low-,medium-,and high-dose groups received 10,20,and 40 mg/kg UA by gavage,respectively,while the control and DR groups received equal volumes of normal saline.Retinal endothelial cells and pericytes were counted and their ratio was calculated u-sing PAS staining.Oxidative stress markers(superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px))were measured by immunoprecipitation.Apoptosis-related proteins(Bcl-2,Bax,caspase-3)and VEGF,COX-2,and MMP-2 protein expression were detected by Western blotting.Results Compared with the control group,the DR group showed significantly increased retinal endothelial cell count,endothelial cell/pericyte ratio,MDA content,and protein expression of Bax,cleaved caspase-3,VEGF,COX-2,and MMP-2,while pericyte count,SOD and GSH-Px activities,and Bcl-2 protein expression were significantly decreased(P<0.05).Compared with the DR group,all groups treated with different doses of UA xhibited reduced en-dothelial cell count,endothelial cell/pericyte ratio,MDA content,and protein expression of Bax,cleaved caspase-3,VEGF,COX-2,and MMP-2,with the high-dose group showing the most pronounced effects.Meanwhile,pericyte count,SOD and GSH-Px activities,and Bcl-2 protein expression were significantly increased in a dose-dependent manner(P<0.05).Conclusion UA protects retinal tissue in DR mice in a dose-dependent manner by downregulating the expression of VEGF,COX-2,and MMP-2,provi-ding a new scientific basis for clinical treatment of DR.