视网膜Sigma-1受体拮抗剂对豚鼠形觉剥夺性近视形成的抑制作用及其机制  

Inhibiting effect of retinal Sigma-1 receptor antagonist on the form deprivation myopia in guinea pigs and its mechanism

作　　者：陈媛媛 谢伏娟[2] 李海波[1] 关宇欣 毛俊峰[1] Chen Yuanyuan;Xie Fujuan;Li Haibo;Guan Yuxin;Mao Junfeng(Eye Center of Xiangya Hospital,Central South University,Changsha 410008,China;Operation Department of Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院眼科中心,眼科学湖南省重点实验室,长沙410008 [2]中南大学湘雅医院手术部,长沙410008

出　　处：《中华实验眼科杂志》2021年第6期477-482,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：湖南省自然科学基金项目(2017JJ2373)。

摘　　要：目的研究视网膜Sigma-1受体拮抗剂N,N-二乙基-2-(4-甲氧基-3-苯乙基氧基苯基)乙胺盐酸盐(NE-100)在豚鼠形觉剥夺性近视(FDM)形成中的调控作用及其机制。方法选取健康21日龄三色豚鼠85只,采用随机数表法将其中36只随机分为正常对照组、眼遮盖14 d组和眼遮盖11 d组,每组12只,其中正常对照组不予遮盖,眼遮盖14 d组用自制半透明眼罩连续遮盖豚鼠右眼14 d作为FDM模型组,眼遮盖11 d组同法连续遮盖右眼11 d后去遮盖3 d。将剩余49只豚鼠采用随机数表法随机分为FDM组10只、FDM+NE-1006μg组12只、FDM+NE-10060μg组10只、FDM+NE-100600μg组9只和FDM+生理盐水组8只。根据分组,FDM眼每天接受球周注射NE-1006μg、60μg、600μg和生理盐水各100μl。采用红外偏心自动验光仪测定眼球屈光度;采用A型超声仪测量眼轴长度;采用角膜曲率计测量角膜曲率。采用免疫组织化学染色和Western blot法检测视网膜中Sigma-1受体蛋白表达分布;采用高效液相色谱电化学法测定神经视网膜的多巴胺含量。结果各组间豚鼠屈光度和眼轴长度总体比较,差异均有统计学意义(F=147.81、160.10,均P<0.01),其中与正常对照组比较,眼遮盖14 d组和眼遮盖11 d组豚鼠遮盖眼相对近视度数明显加深,眼轴明显延长,差异均有统计学意义(均P<0.05);与眼遮盖14 d组比较,眼遮盖11 d组相对近视度数明显较低,眼轴较短,差异均有统计学意义(均P<0.05)。正常对照组豚鼠Sigma-1蛋白表达于视网膜神经节细胞(RGCs)、光感受器内节及少量内核层细胞;与正常对照组比较,眼遮盖14 d组豚鼠RGCs及光感受器内节Sigma-1蛋白染色增强,内核层Sigma-1染色阳性细胞明显增多,内、外丛状层也可见Sigma-1染色阳性细胞,Müller细胞染色尤为明显,在视网膜中Sigma-1受体蛋白表达量明显升高。与眼遮盖14 d组比较,眼遮盖11 d组遮盖眼视网膜中Sigma-1受体蛋白表达量明显下降,差异有统�Objective To investigate the role and mechanism of retinal Sigma-1 receptor antagonist N,N-diethyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethanaminehydrochloride(NE-100)in the formation of form deprivation myopia(FDM)in guinea pigs.Methods Eighty-five 21-day-old guinea pigs were selected,and 36 of them were randomly divided into normal control group,occluded 14-day group and occluded 11-day group,with 12 in each group.The right eyes of guinea pigs in the occluded 14-day group were covered with translucent eye shield for consecutive 14 days,and guinea pigs in the occluded 11-day group were treated in the same way for consecutive 11 days plus 3 days without cover,and guinea pigs in the normal control group were not covered.The other 49 guinea pigs were randomly divided into FDM group(n=10),FDM+NE-1006μg group(n=12),FDM+NE-10060μg group(n=10),FDM+NE-100600μg group(n=9),and FDM+saline group(n=8).The right eyes in each group received 100μl peribulbar injection of NE-1006μg,60μg and 600μg or saline once a day according to grouping.Ocular refraction and axial dimensions were measured using eccentric infrared photorefractor and A-scan ultrasonography,respectively.Corneal curvature was measured with keratometer.Immunohistochemical staining and Western blot were used to detect the expression levels of Sigma-1 receptor protein,and retinal dopamine content was evaluated by high-performance liquid chromatography with electrochemical detection.This study was approved by an Ethics Committee of the Department of Laboratory Animal Science of Central South University(No.2020sydw0084).The use and care of experimental animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals in China.Results There were statistical significant differences in diopter and axial length among the normal control group,occluded 14-day group and occluded 11-day group(F=147.81,160.10;both at P<0.01).Compared with the normal control group,the relative myopia was the deepest and the axial length was the longest in

关 键 词：Sigma-1受体 形觉剥夺 近视 视网膜 多巴胺 豚鼠 

分 类 号：R778.11[医药卫生—眼科]