血管抑素对高氧诱导的视网膜新生血管模型鼠中细胞外信号调节激酶和转录激活蛋白表达的影响  

Inhibitory effects of angiostatin on activities of ERK,AP-1 of experimental retinal neovascularization induced by oxygen

作　　者：孙旭芳[1] 曾水清[2] 张虹[1] 项楠[1] 杨红[1] 李小青[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院眼科,湖北武汉430030 [2]华中科技大学同济医学院附属协和医院眼科,湖北武汉430022

出　　处：《中国现代医学杂志》2006年第14期2126-2128,共3页China Journal of Modern Medicine

摘　　要：目的研究高氧诱导的视网膜新生血管模型鼠中血管抑素对细胞外信号调节激酶(ERK)和转录激活蛋白(AP-1)表达的影响。方法高浓度氧诱导C57BL/6J小鼠建立视网膜缺血性病变动物模型。将30只小鼠分为5组:正常组;高氧对照组;实验I组;实验II组;实验III组,前两组玻璃体内注射生理盐水2μL,后三组玻璃体内分别注射不同浓度的血管抑素2μL。于鼠龄17d取各组小鼠视网膜及前增生的血管膜,免疫印迹(westernblot)实验检测ERK-1的表达,凝胶电泳迁移率改变实验(EMSA)法检测AP-1的表达。结果与正常组相比,鼠龄17d的高氧对照组小鼠ERK-1蛋白表达增高了1.8倍,在实验I组、II组及III组,不同浓度血管抑素可使ERK表达分别降低29.7%(P<0.05)、39.3%(P<0.05)、69.9%(P<0.05),且随着剂量的加大,抑制ERK-1蛋白表达作用逐渐加强,各组之间的差异都有显著性(P<0.05)。与正常组相比,鼠龄17d的高氧对照组小鼠AP-1蛋白表达增高了4.8倍,在实验I组、实验II组、实验III组,血管抑素可使其表达分别降低42.8%(P<0.05)、47.9%(P<0.05)、90.1%(P<0.05),随着剂量的加大,抑制AP-1蛋白表达作用逐渐加强,但实验I组与II组相比差异没有显著性(P>0.05),实验I组与III组、实验II组与III组差异有显著性(P<0.05)。结论血管抑素抗血管新生作用机制可能为抑制ERK通路。[Objective] To observe the inhibitory effects of angiostatin on the activities of ERK, AP-1 of experimental retinal neovascularization induced by oxygen. [Methods] Mouse models of hyperoxia-induced ischemic retinopathy were established. Angiostatin or NS were injected into the vitreous in 5 groups： normal, control and various doses. Fibrovascular tissues were obtained from 17 day-old mice in different groups. The expression of ERK protein was studied by westemblot. The expression of AP-1 was studied by EMSA. [Results] Western-blot analysis demonstrated： ERK activation was reduced markedly after treatment of angiostatin. ERK activation was reduced by 29.7% （P 〈0.05）, 39.3% （P 〈0.05）, 69.9% （P 〈0.05） respectively. EMSA demonstrated： the expression of AP-1 was reduced markedly after treatment of angiostatin. AP-1 activation was reduced by 42.8% （P 〈0.05）, 47.9% （P 〈0.05）, 90.1% （P 〈0.05） respectively. [Conclusions] The mechanism of the inhibitory effect of angiostatin on the proliferation of retinal vessel is to diminish activation of ERK.

关 键 词：血管抑素 新生血管形成 高氧 

分 类 号：R774.1[医药卫生—眼科]