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α-黑素细胞刺激素抑制氧诱导视网膜病变小鼠视网膜新生血管的生成 被引量:2

α-Melanocyte-stimulating hormone inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy
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摘要 背景视网膜新生血管形成(RNV)可发生于多种眼病,导致视网膜出血甚至脱离,抑制病理性RNV已逐渐成为眼科疾病治疗中的重点。α-黑素细胞刺激素(α-MSH)对视网膜发育过程中的生理性血管生成有抑制作用,但其在病理性RNV方面的作用尚未见报道。目的以氧诱导视网膜病变(OIR)小鼠为模型,研究玻璃体腔注射不同质量浓度的α-MSH对病理性RNV的作用。方法选取健康清洁级7日龄C57BL/6J幼鼠40只,应用随机数字表法随机分为OIR+0.33μg/μl α-MSH组、OIR+1.67μg/μl α-MSH组、OIR+3.30μg/μl α-MSH组、OIR组和正常对照组,每组8只。不同剂量α-MSH干预组和OIR组幼鼠在氧体积分数(75±2)%的高氧环境下饲养5d,然后在普通空气环境中饲养5d,正常对照组幼鼠则在普通空气环境中饲养10d。各组取17日龄鼠,球后静脉注射高相对分子质量异硫氰酸葡聚糖(FITC—dextran),制备视网膜铺片,观察视网膜的血管形态,计算无灌注区面积相对于整个视网膜的面积。对小鼠眼球行石蜡切片和苏木精-伊红染色,计数突破内界膜突入玻璃体腔的血管内皮细胞核数。结果视网膜铺片结果显示,正常对照组、OIR组、OIR+0.33μg/μl α-MSH组、OIR+1.67μg/μl α-MSH组和OIR+3.30μg/μl α-MSH组视网膜无灌注区相对面积分别为(0.00±0.00)%、(23.01±3.39)%、(18.14±7.20)%、(15.64±7.07)%和(7.62±6.52)%,各组间视网膜无灌注区相对面积总体比较,差异有统计学意义(F=19.635,P〈0.05);其中OIR组无灌注区相对面积显著高于OIR+3.30μg/μl α-MSH组,差异有统计学意义(t=4.293,P〈0.01)。组织病理学检查结果显示,正常对照组、OIR组、OIR+0.33μg/μl α-MSH组、OIR+1.67μg/μl α-MSH组和OIR+3.30μg/μl α-MSH组突入玻璃体腔的血管内皮细胞� Background Retinal neovascularization (RNV) occurs in multiple eye diseases ,which can lead to bleeding and retinal detachment. Therefore,inhibition of pathological RNV is becoming crucial to the treatment of ocular diseases. Research has shown that α-melanocyte-stimulating hormone (a-MSH) inhibits retinal angiogenesis during physiological development;however,the effects of α-MSH on pathological RNV remain unknown. Objective This study was to investigate the effects of intravitreal injection of α-MSH at different concentrations on pathological RNV in a mouse model of oxygen-induced retinopathy (OIR). Methods Forty healthy clean C57BL/6J mice were randomly divided into OIR+0. 33 μg/μl α-MSH, OIR+ 1.67 μg/μl α-MSH, OIR±3.30 μg/μl α-MSH, OIR, and normal control groups at postnatal day 7 (P7), with 8 pups in each group. The α-MSH intervention groups and OIR group were exposed to high oxygen (75±2)% for 5 days, then maintained under normal air condition for another 5 days;whereas the normal control group was raised under normoxia for 10 days. Retro-orbital injection of high molecular weight fluorescein isothiocyanate-dextran (FITC-dextran) was performed on P17 mice. The retina whole mounts were prepared to reveal retinal vasculature and quantify relative area of vessel obliteration. The mouse eyeballs were subjected to paraffin sections and hematoxylin-eosin staining,and the average number of pre-retinal nuclei per section was quantified. Results FITC-dextran labeled retinal whole mounts showed that the relative vessel obliteration area in normal control,OIR,OIR±0. 33 μg/μl α-MSH,OIR+1. 67 μg/μl α-MSH,and OIR+3.30 μg/μl α-MSH groups were (0. 00±0.00 ) %, (23.01 ±3.39 ) %, ( 18. 14±7.20 ) %, ( 15.64±7.07 ) %, and (7.62 ±6.52 ) %, respectively. There was a statistical significance in the relative avascular area among the groups (F = 19. 635, P〈0. 05 ). The relative avascular area in the OIR group was significantly higher than that in
出处 《中华实验眼科杂志》 CAS CSCD 北大核心 2016年第12期1072-1076,共5页 Chinese Journal Of Experimental Ophthalmology
基金 教育部博士点基金(20121202120005) 教育部留学回国基金(第45批)
关键词 氧诱导视网膜病变 视网膜新生血管 Α-黑素细胞刺激素 Oxygen-induced retinopathy Retinal neovascularization α-Melanocyte-stimulating hormone
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