血管抑素玻璃体注射对糖尿病大鼠视网膜及虹膜血管渗漏的影响  

The effect of angiostatin intravitreal injection on vascular leakage in retina and iris of experimental diabetic rats

作　　者：司马晶[1] Ma Jianxing 郭疆[1] Zhang Sarah X 

机构地区：[1]南方医科大学附属深圳医院暨深圳市第二人民医院眼科,广东518035 [2]Department of Medicine, Department of Cell Biology, The University of Oklahoma Health Science Center,Oklahoma City, OK 73104,U.S.A.

出　　处：《中国实用眼科杂志》2007年第9期1051-1054,共4页Chinese Journal of Practical Ophthalmology

基　　金：2004年深圳市科技计划项目（基金编号200405097）

摘　　要：目的 探讨血管抑素（Angiostatin）玻璃体腔注射对糖尿病大鼠视网膜、虹膜血管渗漏性的影响及其机理。方法 Brown Norway大鼠48只。静脉注射链唑霉素（Streptozotocin，STZ）建立糖尿病模型，随机分为3组（每组糖尿病鼠与正常鼠各8只）。甲组：右眼玻璃体腔注射磷酸盐缓冲生理盐水（Phosphate Buffered Saline，PBS）5山，左眼不注射；乙组、丙组：右眼玻璃体腔注射血管抑素7．5μg／5μl，左眼注射等量PBS；甲、乙组用埃文斯蓝微血管渗透性检测法检测视网膜和虹膜的血管渗透性。丙组用Western blot免疫印迹分析法检测视网膜血管内皮生长因子（Vascular Endothelial Growth Factor，VEGF）的表达。结果 糖尿病鼠较正常鼠的视网膜（P〈0．01）和虹膜（P〈0．05）的血管渗透性增加；糖尿病鼠血管抑素注射眼与对侧PBS注射眼相比，视网膜（P〈0．01）和虹膜（P〈0．05）血管渗透性降低；正常鼠注射血管抑素眼与对侧注射PBS眼相比，视网膜和虹膜血管渗透性无明显改变（P〉0．05）Western blot显示血管抑素显著降低了糖尿病鼠视网膜的VEGF水平，但对正常鼠无影响。结论 血管抑素可明显降低糖尿病鼠视网膜、虹膜血管渗透性，但对正常鼠影响不明显。血管抑素可下调糖尿病鼠视网膜VEGF的表达从而阻断其血管渗漏。因此预测血管抑素对糖尿病黄斑水肿、黄斑囊样水肿、葡萄膜炎等血管渗漏性疾病可能具有潜在的治疗价值。Objective To probe into the effect of an intravitreal injection of angiostatin on vascular leakage in retina and iris of the diabetic rats and study its possible mechanism. Methods Diabetes model was induced in 24 rats by an intravenous injection of STZ （streptozotocin） during 48 Brown Norway adult rats. Three groups were randomization distributed of them. There were 8 of both normal and diabetic rats each group. ST-Z-diabetic rats and age-matched normal rats received an intravitreal injection of 5 μl of sterile PBS （Phosphate Buffered Saline） into the right eye, and the left eye was non-injected in the group A, Angiostatin was injected into the vitreous of the right eye, and the left eye received the same volume of sterile PBS as the control in the group B and group C. The vascular permeability of retina and iris was measured using the Evans blue method in the groupA and groupB. Expression of VEGF in retina was evaluated using western blot analysis in the groupC. Results Diabetic rats showed significant increases of vascular permeability in the retina （P〈0.01 ） and iris （P 〈0.05）. Angiostatin-injected eyes showed significant decreases in vascular permeability in the retina （P〈0.01） and iris （P〈0.05） comparing with the PBS-injected eyes in STZ-diabetic rats. In contrast, intravitreal injection of the same dose of angiostatin into the age-matched normal rats did not result in any significant reduction in vascular permeability in the retina and iris, when compared with the contralateral eye with PBS injection （P〉0.05）. Angiostatin injection significantly reduced VEGF level in the retinas of STZ-diabetic rats but did not affect retinal VEGF level in normal rats. Conclusions Angiostatin significantly reduce pathological vascular perme- ability in the retina and iris of STZ-diabetic rats but not in normal rats. Angiostatin down-regulates VEGF expression and thus, blocks the major cause of vascular leakage in the diabetic retina. Therefore, angiostatin may have a therapeutic poten

关 键 词：血管抑素 血管生成抑制因子 糖尿病视网膜病变 血管内皮生长因子 玻璃体注射 

分 类 号：R587.1[医药卫生—内分泌]