0．004％曲伏前列腺素滴眼液和2％毛果芸香碱滴眼液联合应用对正常兔降眼压效果的评价

Pilot study on hypotensive effect of combination of 0. 004% travoprost with 2% pilocarpine on normal albino rabbit

背景拟胆碱能药物和前列腺素类似物分别用于治疗原发性闭角型青光眼和开角型青光眼的临床效果已被证实，临床上二者常联合用药治疗青光眼，但理论上二者对睫状肌的作用机制是相背离的，因此有必要对二者联合用药的效果和作用机制进行进一步探讨。目的观察联合应用质量分数0．004％曲伏前列腺素和质量分数2％毛果芸香碱的降眼压效果。方法将正常无色素兔30只以随机数字表法随机分为毛果芸香碱组、曲伏前列腺素组和联合用药组3个组，每只兔任意选择一侧眼作为实验眼，分别每日3次点用2％毛果芸香碱滴眼液或每晚1次0．004％曲伏前列腺素滴眼液，联合用药组按上述用法同时点用上述两种药物；对侧眼点用生理盐水为对照眼。各组动物于用药前1d 8：00时以Perkins手持式压平眼压计测量双眼眼压作为基线眼压，并分别于用药后第1、2、4、8、14和24天的8：00时测量双眼眼压，以点眼前后眼压的变化作为主要观测指标。结果毛果芸香碱组、曲伏前列腺素组和联合用药组点眼后1d的眼压均明显低于基线眼压，而对照眼点眼前后眼压无明显变化；各实验眼治疗后各时间点间眼压无明显变化。毛果芸香碱组、曲伏前列腺素组和联合用药组实验眼眼压在点眼前与对照眼相比无明显差异，但点眼后均明显低于对照眼，差异均有统计学意义（P〈0．05）。与各组基线眼压比较，毛果芸香碱组、曲伏前列腺素组和联合用药组的实验眼眼压分别降低了17．5％～22．0％、23．8％～26．4％和27．6％～32．0％。对正常眼来说，联合用药组降眼压作用最强，其次依次为曲伏前列腺素和毛果芸香碱。结论联合用药的降眼压效果比单独点用毛果芸香碱和曲伏前列腺素的效果要好，但小于单独滴用毛果芸香碱和曲伏前列腺素的降眼压幅度之和。

Background It has been clarified that topical administration of cholinomimetie drug or prostaglandin analogus can effectively low intraoeular pressure （IOP） in primary angle-closure glaucoma and angleopen glaucoma,respectively. The two eyedrops are often combined clinically to treat glaucomatous eye. But their effect mechanism on ciliary muscle is different. It is necessary to prove the clinical efficacy of combination of these two drugs. Objective This study attempted to compare hypotensive effect of individual and combinative use of 2% pilocarpine and 0. 004% travoprost in normal rabbit eyes. Methods Thirty normal albino rabbits were randomly divided into three parallel groups. Lateral eye of each rabbit was appointed as the experimental eye and the fellow eye was used as control eye. 2% Piloearpine eyedrop was instilled three times daily and 0. 004% travoprost eyedrops was used once per night in the pilocarpine and travoprost group. These two drugs were combined in the combination group. The normal saline solution was used in the control eyes. IOP was measured bilaterally with Perkins application tonometer at 8：00 am on the day before and 1,2,4,8,14,24 clays after the administration of eyedrops. The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission. Results The IOP was significantly lower on 1 day after use of eyedrops than baseline IOP in the experimental eyes in the pilocarpine group ,travoprost group and combination group ,but no obvious change in IOP before and after use of eyedrops in the control eyes. There was no significant difference in the baseline IOP in both experimental eyes and control eyes,however,significant differences were seen in various time points after administration of eyedrops between experimental eyes and control eyes （P〈0. 05 ）. Compared with baseline IOP, IOP declined by 17.5% - 22.0% in pilocarpine group, 23.8% - 26.4% travoprost group, 27.6% - 32.0% in the combination group. For normal eye,pilocarpine＋travoprost showed a more power lowing IOP effect. Conclusions Hypotensive effect of combinative use of 2% pilcoarpine and 0. 004% travoprost is strongest in comparison with individual use of pilocarpine or travoprost,but less than the statistical sum of individual use of these two drugs in a 24-day duration in normal eye of albino rabbit.