张顺华;赵家良;刘小力;毛进;卞爱玲;
ZHANG Shun-hua;ZHAO Jia-liang;LIU Xiao-li;MAO Jin;BIAN Ai-ling;Department of Ophthalmology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;

• 1:中国医学科学院北京协和医学院北京协和医院眼科

摘要(Abstract)：

目的通过形态学观察的方式探讨单独及联合使用前列腺素衍生物曲伏前列腺素与胆碱能药物毛果芸香碱对葡萄膜巩膜房水外流途径的影响。方法 28只正常无色素兔随机选取4只为对照组,24只随机分为毛果芸香碱组、曲伏前列腺素组和联合用药组,每组8只。对照组在双眼滴用生理盐水1 d时以及3个药物处理组分别在使用2%毛果芸香碱、0.004%曲伏前列腺素、2%毛果芸香碱+0.004%曲伏前列腺素后7、14和24 d时各处死无色素兔2只,摘取双眼眼球,通过HE染色和抗平滑肌抗体染色在光镜下观察兔眼睫状肌纵形肌形态、肌间隙;对照组在双眼滴用生理盐水1 d时以及3个药物处理组在用药24 d时各处死无色素兔2只,在电镜下观察兔眼睫状肌细胞及细胞外胶原束的形态结构。结果单独使用毛果芸香碱组兔睫状肌细胞间隙减小,单独使用曲伏前列腺素组兔睫状肌细胞间隙增大。联合用药组睫状肌纵行肌细胞前1/3排列紧密,肌间隙减小,与单独使用毛果芸香碱组相似,后2/3肌细胞疏松,肌细胞间隙与单独使用曲伏前列腺素组相似;联合用药组睫状肌细胞间胶原的分解情况比单独用曲伏前列腺素组明显。结论联合用药与单独使用曲伏前列腺素比较后部睫状肌间隙无变化,还可能因为增加细胞外胶原分解程度而增加这一途径的房水外流。
Objective To investigate morphological change of uveoscleral outflow pathway after travoprost and pilocarpine are given alone or in combination.Methods Of 28 normal albino rabbits,4 were randomly selected as the control group( treated with normal saline for one day),and the remaining 24 rabbits were divided into three parallel groups and treated with 2% pilocarpine( 3 times per day),0.004% travoprost( per night),and their combination.On the 7th,14th,and 24th day of the treatment,2 rabbits in each drug-treated group were executed.Two rabbits in the control group were executed after treated with normal saline for one day.Eyeballs taken from these rabbits were fixed,and then the pathological specimens were prepared with hematoxylin-eosin( HE) staining and smooth muscle antibody( SMA) immunohistochemical staining.The morphological changes of ciliary smooth muscle and intracellular space were observed with optical microscope.Two normal rabbits from the control group were executed after normal saline treated for 1 day and 2 normal rabbits in each drug-trea-ted group were executed after 24 days of treatment.All eyes of these rabbits were taken and emission electronic microscope specimens were made to observe the microstructure of ciliary muscle and extracellular matrix( ECM).Results Specimens of pilocarpine group showed the contraction of ciliary muscle.Specimens of travoprost group showed the relaxation of ciliary muscle,enlargement of the extracellular space,and decompose of ECM.Specimens of the combination group showed the contraction of anterior 1 /3 part of ciliary muscle but the relaxation of posterior 2 /3 part of ciliary muscle.Decomposition of ECM was more distinct in combination group than those of individual groups.Conclusions Compared with pilocarpine alone or travoprost alone,the combination of these two drugs does not increase the resistance of uveoscleral outflow pathway and probably can promote the aqueous fluid outflow by increasing the decomposition of ECM.

关键词(KeyWords)： 前列腺素类似物;毛果芸香碱;联合用药;葡萄膜巩膜途径
prostaglandin F 2α analogus;pilocarpine;combination;uveoscleral outflow pathway

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 张顺华;赵家良;刘小力;毛进;卞爱玲;
ZHANG Shun-hua;ZHAO Jia-liang;LIU Xiao-li;MAO Jin;BIAN Ai-ling;Department of Ophthalmology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;

参考文献(References)：

• [1]Schachtschabel U,Lindsey JD,Weinreb RN.The mechanism of action of prostaglandins on uveoscleral outflow[J].Curr Opin Ophthalmol,2000,11:112-115.
• [2]Zhang X,Wang N,Schroeder A,et al.Expression of adenylate cyclase subtypesⅡandⅣin the human outflow pathway[J].Invest Ophathalmol Vis Sci,2000,41:998-1005.
• [3]Toris CB,Alm A,Camras CB.Latanoprost and cholinergic agonists in combination[J].Surv Ophthalmol,2002,47:S141-S147.
• [4]Wu LL,Huang P,Gao YX,et al.A 12-week,doublemasked,parallel-group study of the safety and efficacy of travoprost 0.004%compared with pilocarpine 1%in Chinese patients with primary angle-closure and primary angle-closure glaucoma[J].J Glaucoma,2011,20:388-391.
• [5]Toor A,Chanis RA,Polikoff LA,et al.Additivity of pilocarpine to bimatoprost in ocular hypertension and early glaucoma[J].J Glaucoma,2005,14:243-248.
• [6]Zhang SH,Zhao JL,Liu XL,et al.Pilot study on hypotensive effect of combination of 0.004%travoprost with 2%pilocarpine on normal albino rabbits[J].Chin J Exp Ophthalmol,2012,9:774-778.
• [7]Lütjen-Drecoll E,Tamm E.Morphological study of the anterior segment of cynomolgus monkey eyes following treatment with prostaglandin F2 alpha[J].Exp Eye Res,1988,47:761-769.
• [8]喻应贵,孙乃学,王建明.匹罗卡品对兔眼葡萄膜巩膜途径作用的形态学研究[J].中国实用眼科杂志,2001,19:528-530.
• [9]Bill A.Conventional and uveo-scleral drainage of aqueous humour in cynomolgus monkeys[J].Exp Eye Res,1966,5:45-54.
• [10]Kaufman PF.Assessment of ocular hypotensive mechanisms and additivity of antiglaucoma drugs in humans[J].Arch Ophthalmol,1999,117:673-674.
• [11]Yousufzai SY,Zheng P,Abdel-Latif AA.Muscarinic stimulation of arachidonic acid release and prostaglandin synthesis in bovine ciliary muscle:prostaglandins induce cyclic AMP formation and muscle relaxation[J].Exp Eye Res,1994,58:513-522.