氟他胺诱导干眼模型大鼠角膜和泪腺组织病理变化及TNF-α、IL-1α的表达  

Pathological changes of cornea and lacrimal glands in dry eye rat model induced by flutamide and expression of TNF-α and IL-1α

作　　者：彭玲[1] 蔡伟浩 陆晓和[1] 钟彦彦[1] 易锐文 

机构地区：[1]南方医科大学珠江医院眼科,广东省广州市510282

出　　处：《眼科新进展》2016年第6期506-511,共6页Recent Advances in Ophthalmology

基　　金：国家自然科学基金面上项目(编号:81371067);广东省自然科学基金(编号:S2013040013713);广东省科技计划项目(编号:2102B061700106)~~

摘　　要：目的通过雄激素受体拮抗剂氟他胺溶液灌胃建立大鼠干眼模型,观察干眼大鼠角膜及泪腺组织病理变化及TNF-α、IL^(-1)α的表达。方法取32只SPF级SD雌性大鼠随机分为4组,氟他胺高、中、低浓度组和对照组,每组8只,每天分别用浓度为16 mg·kg-1、13 mg·kg-1、10 mg·kg-1氟他胺溶液和1 m L生理盐水灌胃。给药后0周、2周、4周、8周、16周、20周分别检测各组基础泪液分泌试验(SchirmerⅠtest,SⅠt)值、泪膜破裂时间(break-up time,BUT)及角膜荧光素钠染色情况。给药后0周、10周、20周采用放射免疫法检测各组血清睾酮浓度。给药后20周处死大鼠取各组角膜与泪腺组织行病理学观察,免疫组织化学方法检测各组TNF-α、IL^(-1)α的表达情况。结果给药后4周时高、中浓度组SⅠt值开始减小,与对照组比较差异均有统计学意义(均为P<0.05)。8周时高、中、低浓度组的SⅠt值均小于对照组(均为P<0.05),20周时高(3.23±0.31)mm、中(3.98±0.36)mm、低(4.73±0.18)mm浓度组的SⅠt值进一步减小,且均较对照组(9.60±0.60)mm下降大于50%(均为P<0.05),高、中、低浓度组两两比较差异均有统计学意义(均为P<0.05)。给药后4周时高浓度组大鼠即出现BUT缩短,8周时,高、中、低浓度组的BUT均短于对照组(均为P<0.05),20周时高(2.40±0.61)s、中(4.32±0.68)s、低(6.10±0.81)s浓度组的BUT较对照组(9.12±0.73)s进一步缩短,各组之间两两比较差异均有统计学意义(均为P<0.05)。给药后4周时高、中浓度组开始出现角膜上皮点状荧光素钠着色,16周时中、低浓度组出现小片状着色,高浓度组可见角膜上皮弥漫性大片状着色,20周时各组染色评分两两比较差异均有统计学意义(均为P<0.05)。给药后20周时睾酮浓度高浓度组(5.08±0.21)pg·m L^(-1)、中浓度组(4.23±0.16)pg·m L^(-1)、低浓度组(3.58±0.24)pg·m L^(-1)较对照组(2.24±0.15)pg·m L^(-1)不同程度升高,与对照组比较差异�Objective To establish the dry eye rat model induced by flutamide,observe the pathological changes of cornea and lacrimal glands and the expression of tumor necrosis factor-α（TNF-α）,interleukin-1α（IL-1α）.Methods Thirty-two specific pathogen free SD rats were randomly divided into four groups（8 cases in each group）：high,medium,low concentration group and control group,were respectively irrigated stomach with flutamide solution on concentration of 16 mg ·kg^-1,13 mg ·kg^-1,10 mg ·kg^-1 and 1 mL saline solution every day.Each group on week 0,2,4,8,16,20 were evaluated the Schirmer Ⅰ test（SⅠt）,tear break-up time（BUT） and corneal fluorescence staining.Each group on week 0,10,20 were measured serum testosterone levels by radioimmunoassay.The animals in each group were sacrificed on week 20,the cornea and lacrimal gland were taken to perform the histopathological observation,and the immunohistochemistry method was used to detect the expression of TNF-α and IL-1α.Results On week 4,SⅠt values of high,medium concentration groups began to decrease,there were statistical difference compared with control group（all P〈0.05）.On week 8,SIt values of high,medium,low concentration groups were all lower than that of control group（all P〈0.05）;On week 20,SⅠt values of high,medium,low concentration group were（3.23 ± 0.31） mm,（3.98 ±0.36） mm,（4.73 ±0.18） mm,respectively,which were further shortened,compared with control group（9.60 ± 0.60） mm all decreased more than 50%,and there were significant differences among high,medium,low concentration groups（all P〈0.05）.On week 4,BUT of high concentration group began to shorten;On week 8,BUT of high,medium,low concentration groups were shorter than control group（allP〈0.05）;On week 20,BUT of high,medium,low concentration groups were（2.40 ±0.61） seconds,（4.32 ± 0.68） seconds,（6.10 ±0.81） seconds,which were all lower than control group（9.12 ±0.73） seconds,there were statistical differences among e

关 键 词：干眼动物模型 雄激素受体拮抗剂 氟他胺 肿瘤坏死因子-α 白细胞介素-1Α 

分 类 号：R285.5[医药卫生—中药学]