鱼精蛋白对糖尿病模型大鼠眼玻璃体和血清中血管内皮细胞生长因子表达的影响  

Effect of Protamine on VEGF Expression in Vitreous and Serum of Rats with Diabetic

作　　者：杨吟[1] 潘雪菲[1] 彭洁[1] 胡建斌[1] 

机构地区：[1]四川省医学科学院.四川省人民医院眼科,成都610072

出　　处：《四川大学学报（医学版）》2012年第1期46-49,共4页Journal of Sichuan University(Medical Sciences)

基　　金：四川省卫生厅(项目编号000105);四川省人事厅出国留学人员支撑项目资助

摘　　要：目的探讨鱼精蛋白对糖尿病模型大鼠眼玻璃体和血清中血管内皮细胞生长因子(vascularendothelial growth factor,VEGF)表达的影响。方法 110只Wistar大鼠,随机选10只为空白对照组,其余100只大鼠行链脲佐菌素腹腔注射建立糖尿病模型,造模成功后分为糖尿病模型组和鱼精蛋白治疗组。模型组再分为观察1、2、3、4、5月亚组(M1、M2、M3、M4、M5组),治疗组分为治疗1次、2次和3次亚组(T1、T2和T3组)。T1组大鼠在造模3月后行双眼玻璃体腔注射鱼精蛋白1次,T2组在造模3、4月后分别行双眼玻璃体腔注射鱼精蛋白,共2次,T3组在造模3、4、5月后分别行双眼玻璃体腔注射鱼精蛋白,共3次,每次50μg,5μL。各治疗组大鼠均在注药结束1周后处死,以酶联免疫吸附法检测血清中和左眼玻璃体中VEGF蛋白的含量,并摘取右眼石蜡包埋作病理切片,行HE染色,观察视网膜形态学改变。结果观察期内糖尿病大鼠眼玻璃体和血清中VEGF的表达逐渐升高(P<0.05);经鱼精蛋白注射2次后的大鼠,其玻璃体中VEGF的表达较未注药组降低(P<0.05),且治疗3次后降低更明显(P<0.01);而治疗组血清中VEGF的表达较相应时间模型组大鼠无明显变化。大鼠视网膜HE染色可见糖尿病模型组视网膜内层增厚,局部中断、内外核层细胞排列紊乱,出现血管增殖,而治疗组视网膜病变明显好转。结论鱼精蛋白作为一种有效的VEGF抑制剂,经玻璃体腔注射,可能为治疗糖尿病视网膜新生血管及眼部其他新生血管提供新的药物选择。Objective To study the effect of protamine on vascular endothelial growth factor（VEGF） expression in vitreous and serum of rats with diabetic.Methods 110 rats were included in the study,with 10 rats for normal control and the other 100 for diabetic models that induced by Streptozocin intraperitoneal injection.Then 80 rats with diabetic were used as eight groups： three groups（T1,T2 and T3） for intravitreal injection of protamine（50 μg protamine in 5 μL）,and the other five groups were used as control.After 3 months,the T1,T2 and T3 group received the first injection;after 4 months,the T2 and T3 group received the second injection;after 5 months,the T3 group received the third injection.The rats were executed one week after their last injection,the retinae of the rats were taken for HE staining,and expression of VEGF in the serum and vitreous were measured by ELISA.Results As diabetic developed,VEGF expression in both serum and vitreous rised（P〈0.05）;after the second protamine injection,VEGF expression in vitreous began to decrease obviously（P〈0.05）;but VEGF expression in the serum didn’t change by protamine.Rat retinal HE staining for the diabetic model group revealed retinal thickening,local interrupt,inner and outer nuclear layer cell derangement and vascular proliferation,which were significantly improved for the treatment groups.Conclusion Intravitreal injection of protamine reduced VEGF expression in vitreous of rats with diabetic,and protamine might be a new treatment for diabetic retinopathy,especially for retinal neovascularization.

关 键 词：糖尿病视网膜病变 视网膜新生血管 血管内皮生长因子 鱼精蛋白 

分 类 号：R587.1[医药卫生—内分泌]