Expression of vascular endothelial growth inhibitor in diabetic retinopathy rats

Objective To observe the expression of vascular endothelial growth inhibitor VEGI.TL1A),vascular endothelial growth factor (VEGF),tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in diabetes rats' serum,vitreous and retina,and discuss the role of VEGI in the pathogenesis of diabetic retinopathy (DR).Methods A total of p70 adult male Wistar rats were randomly divided into 4 groups,the control group (10 rats),the diabetes mellitus (DM) 1 month group (20 rats),the DM 3 month group (20 rats) and the DM 6 month group (20 rats).Cytokines of serum and vitreous were determined by enzyme-linked immunosorbent assay (ELISA),and the concentrations of the cytokines in the retina were determined by immunohistochemistry on paraffin retinal sections.Hematoxylin-eosin (HE) staining of retina was used to estimate the pathological change of DR.The results were analyzed by one-way analysis of variances,independent samples t-test and LSD test.Results The serum TL1A levels of the control group,the DM 1 month group,the DM 3 month group and the DM 6 month group rats were (92.09 ±2.05),(118.364±8.30),(85.904±7.51) and (78.904±4.88) ng/L respectively,the level of TL1A in serum of the DM 1 month group,the DM 3 month group and the DM 6 month group were significantly lower than that of the control group (F=77.405,P＜0.05).The concentration of serum TNF-α and IL-1β increased after DM model was established (F=3.508,15.416; P＜0.05); the VEGF level in serum showed no difference between the groups (F=1.242,P＞0.05).The vitreous TL1A levels of the control group,the DM 1 month group,the DM 3 month group and the DM 6 month group were (91.50±8.18),(67.03±6.74),(47.44±4.92) and (46.01±4.62) ng/L respectively,every DM groups showed significant difference with the control group (F=114.777,P＜0.05); VEGF level in vitreous increased from 1 month after DM model was established (F=8.816,P＜0.05) ; TNF-α and IL-1β level in vitreous also showed an upward tendency (F=4.392,3.635; P＜0.05).Paraffin section immunohistochemistry showed that the absorbance (also called optical density) of TLIA of the DM 1 month group and the DM 3 month group were significantly lower than that of the control group (t=6.851,6.066; P＜0.05),but the DM 6 month group showed no difference with the control group (t=1.401,P＞0.05) ; the level of VEGF and TNF-α in DM groups were higher than that of the control group (tVEGF =-4.709,-16.406,-9.228; tTNF-α =-4.703,-6.583,-17.762; P＜0.05) ; the level of IL-1β were significantly higher in the DM 1 month group and the DM 6 month group (t=-4.108,-3.495; P＞0.05); but the DM 3 month showed no difference with the control group (t=-0.997,P＞0.05).HE staining of retina showed that the retina of the control group and the DM 1 month group had normal retinal structures,the DM 3 month group had retinal edema and disorganization,the DM 6 month group had severe retinal edema,deep stain of ganglion cells,and more neovascularization in inner plexiform layer.Conclusion VEGI is involved in the pathogenesis of DR,and it might interacts with VEGF,TNF-α and IL-1β to affect the development of DR. Key words: Diabetic retinopathy/pathophysiology;  Vascular endothelial growth factors;  Tumor necrosis factor-alpha