| Objective:To explore the effects and mechanism of recombinant human endostatin(rh-ES) on oxygen induced retinopathy by establishing oxygen-induced retinopathy(OIR) animal models.By studying the variations of m RNA of vascular endothelial growth factor(VEGF) and vascular endothelial growth factor receptor-2(VEGFR-2) which are get in rats to investigating the relationship of rh-ES, VEGF, VEGFR-2,high oxygen and retinal neovascularizations.Method:Forty Sprague Dawley rats are randomly divided into normal control group,high oxygen control group,drug intervention group. Each group have 8 rats.Drug intervention group according to the drug dose divided into large dose group,medium dose group,small dose group. Each group have 8 rats. Rats which in the normal control group live in air(oxygen concentration 21%±1%). High oxygen control group and Drug intervention group are placed in a high oxygen environment(oxygen concentration 75%±2%) for 5 days and then put back to air. Drug intervention group are given drug by injection for 5 days when at the age of 12 days. The dose of rh-ES which given to the small dose group is 3mg/ kg/d. To middle dose group is 6mg/kg/d. To high dose group is 9mg/kg/d. In order to observe retinal angiogenesis changes and calculating the number of the endothelial nuclei which breakthrough the retinal internal limiting membrane, each group was randomly collected by HE staining.By the way reverse transcription- polymerase chain reaction(RT-PCR) to test the m RNA levels of VEGF and VEGFR-2 in each group.Results:(1)The number of retinal inner limiting membrane in endothelial cells which is stained by HE in each retinal tissue slice as the normal control group is(0.95±0.06),in high oxygen control group is(23.30 ± 1.75),in small dose group(9.04±0.73), in medium dose group is(6.67 ± 1.02),in large dose group is(2.97 ± 0.31). The number of hyperoxia group breakthrough retinal inner limiting membrane endothelial cells is higher than rh-ES intervention group and normal control group, the difference was statistically significant(P<0.01). In intervention group, the number of retinal inner limiting membrane in endothelial cells were decreased with the increase of the doses, the difference was statistically significant(P<0.01), Rh-ES intervention group compared with the normal control group, the difference was statistically significant(P<0.01).(2) The expressions of VEGF and VEGFR-2 m RNA, high oxygen control group is higher than the normal control group and rh-ES intervention group, The difference was statistically significant(P<0.05), VEGF and VEGFR-2 m RNA relative expression were decreased with dose increasing. The difference was no significant when high dose group compared with the normal control group.(3) The number of endothelial cells and the expression of VEGF and VEGFR-2 m RNA have positive correlationsConclusion:(1)The expression of VEGF and VEGFR-2 m RNA were increased in the model of OIR.(2)The effect of rh-ES on the expression of VEGF and VEGFR-2 m RNA was negative.(3)Rh-ES could inhibit angiogenesis by inhibiting expressions of VEGF and VEGFR-2 m RNA. |
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