摘除泪腺和泪腺注射肉毒杆菌毒素A制备大鼠干眼模型的比较  

Comparison of two methods for establishing rat dry eye model:lacrimal gland extirpation and lacrimal gland injection of botulinum toxin A

作　　者：董子奕[1] 应铭[2] 杨希[3] 马伊 Zi-Yi Dong;Ming Ying;Xi Yang;Yi Ma(Department of Ophthalmology,Tianjin Union Medical Center,Tianjin 300121,China;Tianjin Eye Hospital,Tianjin Key Lab of Ophthalmology and Visual Science,Tianjin 300020,China;Department of Neurology,Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital,Tianjin 300120,China)

机构地区：[1]中国天津市人民医院眼科,300121 [2]中国天津市眼科医院,天津市眼科学与视觉科学重点实验室,300020 [3]中国天津市中医药研究院附属医院脑病2科,300120

出　　处：《国际眼科杂志》2020年第8期1325-1330,共6页International Eye Science

基　　金：天津市人民医院院级课题(No.2016YJ023)。

摘　　要：目的:分别采用摘除泪腺法和泪腺注射肉毒杆菌毒素A法诱导大鼠干眼症模型,通过对比两种干眼症模型的临床表现、病理学特点和细胞因子变化,探讨其优缺点和适用范围。方法:健康8周龄雄性Brown Norway大鼠30只,随机分为3组:A组左眼为空白组,B组摘除大鼠左侧主泪腺,C组左侧泪腺注射肉毒杆菌毒素A。比较实验前1d,实验后3、7、14、28、42d的泪液分泌量(SⅠt)、泪膜破裂时间(BUT)、角膜荧光素钠染色评分的变化。42d观察结膜、角膜和泪腺组织病理学改变;通过实时荧光定量PCR对白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)和上皮生长因子(EGF)表达量进行检测。结果:实验后第3d开始,B、C组均出现泪液分泌量持续性减少,与A组均有差异(P<0.05);实验后第7d开始,B、C组均出现BUT持续性缩短以及角膜上皮染色明显增多,与A组比较有差异(P<0.05);以上临床数据B、C组间比较均无差异(P>0.05)。A组角膜上皮细胞形态正常,B组及C组角膜上皮均存在不同程度表层细胞丝状分离,结膜杯状细胞数目明显减少,C组泪腺组织明显萎缩。B、C组结膜和角膜组织的EGF、TNF-α和IL-6表达量均显著增高,与A组比较均有差异(P<0.05)。B、C组间EGF和TNF-α的表达均无差异(P>0.05);与C组比较,B组中IL-6的表达量更高(P<0.05)。结论:摘除泪腺和泪腺注射肉毒杆菌毒素A均可以构建稳定的水液缺乏型大鼠干眼模型,建议根据实验设计及实验目的去选择合适的动物模型。·AIM:The dry eye model of rat was induced either by lacrimal gland extirpation or injection of botulinum toxin A into lacrimal gland.The clinical manifestations,pathological features and cytokine changes of these two models were compared,then we discussed their advantages,disadvantages and applicable scope.·METHODS:Thirty healthy 8-week-old male Brown Norway rats were randomly assigned into three groups equally.The left eye of group A was blank group,group B was the left lacrimal gland extirpation model,the left tear gland of group C was injected with botulinum toxin A.We compared the data of Schirmer I test,tear break-up time(BUT),and the corneal fluoresceince staining scores at different times(1d before experiment,3d,7d,14d,28d,and 42d after the surgical process).We observed pathological changes of conjunctiva,cornea and lacrimal gland at 42d,and we used real-time polymerase chain reaction to analyze interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and epithelial growth factor(EGF).·RESULTS:At the 3d,compared with group A,the tear secretion of both group B and group C were continuous decrease(P<0.05).At the 7d,compared with group A,the BUT of both group B and group C began to decreased(P<0.05),and the corneal epithelial staining scores of both group B and group C began to significantly increase(P<0.05).There was no statistical difference in the above clinical data between group B and group C(P>0.05).The corneal epithelial cells in group A was set as normal morphology,while the corneal epithelial cells in group B and group C showed filamentous separation of surface cells to varying degrees,and the number of conjunctival goblet cells was decreased.The lacrimal gland of group C was obviously atrophic.In conjunctival and corneal tissues,the expression of EGF,TNF-αand IL-6 were significantly increased in group B and group C,which was statistically significant compared with group A(P<0.05).The expression of EGF and TNF-αdidn’t altered significantly between group B and group C(P>0.05),however,the expression

关 键 词：泪腺 肉毒杆菌毒素A 干眼 水液缺乏型 

分 类 号：R73[医药卫生—肿瘤]