Retinal morphologic change and related factor analysis in rats with early stage of diabetes mellitus

Abstract

Background The pathological foundation of diabetic retinopathy is the breakdown of the bloodretina barrier induced by multifactors.Objective This study was to investigate the retinal morphologic change and the levels of serum vascular endothelial growth factor(VEGF),endothelin(ET)and nitric oxide(NO)in diabetic rats.Methods Forty healthy female SD rats were randomly divided into experimental group and control group and 20 rats for each group.Acute diabetes models were established by the intraperitoneal injection of 60 mg/kg streptozotocin in experimental group and the equal volume of buffer solution was injected at the same way in the control group.The serum VEGF level,ET level and NO concentration of diabetic and control rats were detected using ELISA double antibody sandwich method,125I radioimmune method and nitrate reduction method respectively at 2,4,6 and 8 weeks after injection.The eyeballs of rats were enucleated at the eighth week for retinal pathologic examination.This experiment followed the Measures for the administration of experimental animals of Shanghai City.Results The retinal structure was normal throughout the experimental duration in the control group.However,retinal edema and cellular disorganization appeared at 4 months and retinal blooding could be seen with the extending of diabetes course.The levels of serum VEGF and ET in each experimental group were significantly higher than those in control groups(P＜0.05).The levels of serum NO elevated in 2-month experimental group compared with same-phase control group(Z =-2.193,P＜0.05),and those in 6-and 8-month experimental groups were significantly lower than in corresponding control groups(Z =-2.449,Z =-2.236,P＜0.05).With the progression of the disease,the levels of VEGF and ET increased gradually,but the levels of NO decreased gradually,showing statistically significant differences(P＜0.05).The level of serum VEGF showed a positive correlation with serum ET level and a negative correlation with the serum NO concentration(r=-0.814,r=-0.803,P＜0.01)in the experimental group.A negative leaner relation was also found between serum ET level and serum NO concentration(r=0.821,P＜0.01).Conclusions The serum VEGF,ET and NO levels are closely associated with the degree of retinal lesion in early diabetic models.These results suggest that serum VEGF,ET and NO levels may be the important indexes predicting the course of retinal disease in diabetic rats. Key words: Diabetes mellitus; Retina; Vascular endothelial growth factor; Endothelin; Nitric oxide