罗格列酮对糖尿病大鼠视神经病变的防治作用及其作用机制  

Preventive effects of rosiglitazone against diabetic optical neuropathy

作　　者：喻小龙[1] 周寿红[2] 谭钢[1] 刘二华[1] 

机构地区：[1]南华大学附属第一医院眼科,衡阳421001 [2]南华大学医学院生理学教研室,衡阳421001

出　　处：《中华实验眼科杂志》2013年第9期833-838,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目（81100648）;湖南省科技计划项目（2010FJ4135）;衡阳市科学技术局科技计划项目（2012KJ48）

摘　　要：背景视神经病变是糖尿病严重的眼部并发症之一，过氧化物酶体增生物激活受体1（PPAR~）罗格列酮在缓解糖尿病的发生发展中发挥重要的作用，但其对糖尿病视神经病变的作用机制尚不明确。目的探讨罗格列酮对糖尿病大鼠视神经病变的防治作用及其对视神经组织中神经细胞黏附分子（NCAM）表达的影响。方法将清洁级雄性SD大鼠采用随机数字表法随机分为正常对照组、糖尿病模型组和罗格列酮治疗组，每组各10只。糖尿病模型组和罗格列酮治疗组大鼠采用链脲佐菌素（50mg／kg）尾静脉注射法建立糖尿病大鼠模型，罗格列酮治疗组大鼠在造模后3d开始每日用罗格列酮（5mg／kg）灌胃，共给药4周。于实验末测量大鼠空腹血糖水平，采用ELISA法检测大鼠血浆中血管内皮生长因子（VEGF）水平，用劳克坚牢蓝染色法观察各组大鼠视神经髓鞘的结构变化，采用实时定量PCR和Westernblot法检测大鼠视神经中NCAM的表达。结果罗格列酮治疗4周时正常对照组、糖尿病模型组和罗格列酮治疗组大鼠空腹血糖水平、血浆VEGF质量浓度、视神经组织中NCAMmRNA及其蛋白表达水平的总体比较差异均有统计学意义（F=6．12，P〈0．01；F=5．14，P〈0．05；F=4．75，P〈0．05；F=4．87，P〈0．05）。糖尿病模型组大鼠空腹血糖水平明显高于正常对照组，而罗格列酮治疗组大鼠空腹血糖水平明显低于糖尿病模型组，差异均有统计学意义（t=2．26、2．08，P〈0．05）。糖尿病模型组大鼠血浆VEGF质量浓度为（134．28±11．36）ng／L，明显高于正常对照组的（28．76±4．21）ng／L；罗格列酮治疗组大鼠血浆VEGF质量浓度为（42．67±5．83）ng／L，明显低于糖尿病模型组，差异均有统计学意义（t=2．36、2．17，P〈0．05）。劳克坚牢蓝染色显示，正常对照组大鼠视神经髓鞘组织结构正常，糖尿病模�Background Optic neuropathy is one of the diabetic eye complications. Rosiglitazone, a peroxisome proliferator activated receptor γ （PPARγ）agonist, plays a very important role in arresting the pathogenesis and development of diabetes. However,the role of PPAR~ in diabetic optic neuropathy is unclear. Objective This study was to investigate the protective effect of rosiglitazone against diabetic optic neuropathy and its mechanism. Methods Male Sprague-Dawley rats were randomly divided into the control group,diabetic group and rosiglitazone group,with 10 rats for each group. Diabetic models were induced by injecting 50 mg/kg of streptozotoein via the caudal vein,and rosiglitazone（5 mg/E kg ·d] ）was used in the rats of the rosiglitazone group by intragastric administration every day for four weeks. At the end of the experiment,the fasting blood sugar（FBS） was tested in all the animals. The level of vascular endothelial growth factor（VEGF） in the blood plasma was detected by ELISA. Optical neural tissues were obtained from the rats of each group, and Lauck fast Blue myelin stain was used to examine the morphology of the optical myelin. The expression of neural cell adhesion molecule （NCAM） mRNA and protein in the optic nerve was detected by real time PCR and Western blot,respectively. Results The levels of FBS,blood plasma VEGF,NCAM mRNA and protein in the optic nerve were significantly different among the control group, diabetic model group and the rosiglitazone group after the administration of 5 rag/（ kg ~ d） rosiglitazone for 4 weeks （ F = 6. 12, P〈0.01 ; F = 5.14, P〈0.05 ; F = 4. 75, P〈0. 05 ; F = 4.87, P〈0. 05 ）. Compared with the control group, the level of FBS significantly increased in the diabetic model group （t = 2. 26,P〈0. 05 ） , and that in the rosiglitazone group significantly declined in comparison with the diabetic model group（t= 2. 08 ,P〈0. 05 ）. The optic nerve exhibited a normal morphology in the control group as revealed by the Lauck fast Blue mye

关 键 词：糖尿病 视神经病变 罗格列酮 血管内皮生长因子 神经细胞黏附分子 

分 类 号：R587.2[医药卫生—内分泌] R774.6[医药卫生—内科学]