辛伐他汀对糖尿病大鼠玻璃体及视网膜结缔组织生长因子表达的影响  

Effects of simvastatin on expression of connective tissue growth factor in vitreous and retina of diabetic rats

作　　者：胡艳滨[1] 张静楷[1] 孙智勇[1] 刘玉梅[1] 颜华[1] 

机构地区：[1]天津医科大学总医院眼科,300052

出　　处：《中华眼科杂志》2012年第5期444-449,共6页Chinese Journal of Ophthalmology

基　　金：中国残疾人康复协会视力残疾康复专业委员会科学基金（CARD-14-201001）;天津医科大学科学基金（2010ky27）

摘　　要：目的研究辛伐他汀对糖尿病大鼠玻璃体和视网膜中致纤维化的结缔组织生长因子（CTGF）表达的影响及其安全性。方法实验研究。采用随机数字表法，将40只成年雄性Wistar大鼠分为正常对照组（10只）和糖尿病组（30只）。待糖尿病组大鼠4个月时，根据玻璃体腔注射辛伐他汀与否，再采用随机数字表法将其分为辛伐他汀干预组（20只）和糖尿病阳性对照组（10只）；辛伐他汀干预组眼内注射辛伐他汀，糖尿病阳性对照组不注射任何药物。于实验第7天行视网膜电图（ERG）检查并处死全部大鼠，摘取眼球，用酶联免疫吸附测定法和免疫组织化学检测法，测定大鼠玻璃体和视网膜中CTGF含量及其表达阳性率，用末端脱氧核糖核酸转移酶介导的dUTP缺口末端标记法检测视网膜细胞凋亡指数。组问检测数据比较采用单因素方差分析和LSD—t检验。结果大鼠玻璃体腔注射辛伐他汀后，无全身中毒反应，未见晶状体混浊、眼内炎等眼部病变。辛伐他汀干预组、糖尿病阳性对照组及正常对照组大鼠玻璃体CTGF含量分别为359．21μg／L、478．47μg／L及210．78μg／L，组间比较差异有统计学意义（F=252．366，P〈0．05）；辛伐他汀干预组和糖尿病阳性对照组玻璃体CTGF含量明显高于正常对照组，差异有统计学意义（t=12．123，23．816；P〈0．05）；辛伐他汀干预组玻璃体CTGF含量明显低于糖尿病阳性对照组，差异有统计学意义（t=11．693，P〈0．05）。正常对照组大鼠视网膜CTGF免疫组织化学和细胞凋亡检测结果均为阴性，辛伐他汀干预组和糖尿病阳性对照组大鼠视网膜CTGF表达阳性率分别为（26．60±2．95）％和（42．31±2．59）％，辛伐他汀干预组较糖尿病阳性对照组表达阳性率明显降低，差异有统计学意义（t=12．112，P〈0．05）；辛伐他汀干预组和糖尿病阳性对照组大鼠视Objective To study the effects of simvastatin on the expression of connective tissue growth factor （CTGF） that cause fibrosis in the vitreous and retina after intravitreal injection in diabetic rats, and to explore the safety of this procedure. Methods It was an experimental study. Forty adult male Wistar rats were randomly divided into normal control group （10 rats） and diabetes mellitus group （30 rats）. Four months later, according to whether treated with simvastatin or not, the diabetes mellitus group randomly divided into simvastatin intervention group （20 rats ） and diabetic positive control group （10 rats ）. Simvastatin was injected into the vitreous in the simvastatin intervertion group, but not in the diabetic positive control group. Seven days later, after the examination of electroretinogram （ ERG）, all rats were sacrificed, and their eyeballs were enucleated. Enzyme-linked immunosorbent assay （ELISA） and immunohistochemistry method were performed to determine the expression of CTGF in the vitreous and retina. Terminal DNA transferase-mediated dUTP nick end labeling （TUNEL） method was used to detect apoptosis of retina cells. Concentration of CTGF in the vitreous, retinal expression of CTGF, retinal cellular apoptosis index, ERG-b wave and oscillatory potentials （OPs） of rats in each group were compared using analysis of variance LSD test methods. Results No systemic toxic reactions, no lens opacity and no endophthalmitis occurred after injection of simvastatin into the vitreous of rats. Concentrations of CTGF in vitreous of simvastatin intervention group, diabetes positive control group and normal control group rats were 359. 21 μg/L,478. 47 μg/L and 210. 78 μg/L, respectively（ F = 252. 366 ,P 〈 0. 05 ）. The levels of CTGF in the vitreous of simvastatin intervention group and diabetic positive control group was significantly higher than that of the normal control group and showed significant difference （ t = 12. 123,23. 816 ; P 〈 0. 05 ）. CTGF levels i

关 键 词：糖尿病视网膜病变 糖尿病 实验性 结缔组织生长因子 斯伐他汀 

分 类 号：R77[医药卫生—眼科] R587[医药卫生—临床医学]