0.03%Bimatoprost对正常无色素兔的降眼压机制研究

Experimental study on the mechanism of lowing intraocular pressure of bimatoprost in albino rabbits

目的研究前列腺素类似物的新成员—Bimatoprost的降眼压机制。方法将正常无色素兔双眼滴入0.03%Bimatoprost,按用药时间分为5组,应用酶谱分析法,检测滴用Bimatoprost不同时间后兔眼睫状肌匀浆上清液及房水中基质金属蛋白酶(MMPs)的变化并进行半定量分析;制备不同用药时间的兔眼球病理切片及超薄切片,观察药物对兔眼各层组织及睫状肌细胞的影响。结果随用药时间的延长,MMP-1/2在兔眼睫状肌匀浆上清液中的活性增加,而在房水中则无明显变化。Bimatoprost可引起睫状肌松弛,睫状肌间隙增宽。睫状肌细胞间连接逐渐消失,细胞间隙增大,细胞外基质减少。结论滴用0.03%Bimatoprost后,兔眼睫状肌细胞中的MMPs合成增加,活性增强,睫状肌细胞外基质减少,这些变化可降低葡萄膜巩膜通道的阻力,增加房水外流,构成了Bimatoprost降眼压机制的重要组成部分。

Objective Our previous study showed Bimatoprost has a obvious effect suppressing intraocular pressure （IOP） ,but its active mechanism is worth studing. Our study was to evaluate the mechanism of lowing IOP of 0. 03% Bimatoprost in albino rabbits. Methods Fifty normal albino rabbits were divided into 5 groups randomly based on the duration of medication. 25 μL of 0. 03% Bimatoprost eye drops was administrated topically once per day for 3,7,14 and 21 days, respectively in experimental groups, and the normal saline solution was given at a same way in the control group. The activity of matrix metalloproteinases （MMPs） in rabbit ciliary smooth muscle cells and aqueous humour was assayed after usage of drug using gelatin SDS-PAGE zymography. Bands intensity（ the activity of MMPs） was measured by UVI. The morphology of eye wall and anterior chamber angle after administration of drug was observed by SMA and HE staining. The morphological alterations of ciliary muscle cells,extracellular space and MMPs were examined under the transmission electron microscope. Results After treated with 0. 03% Bimatoprost,the activity of MMP-1/2 in ciliary muscle increased by 23.43% ,64. 69% ,89.30% and 119.66% in 3,7,14 and 21 days respectively after administration of drug, but that in aqueous humor was unchanged. The ciliary smooth muscle was relaxed and intercellular space of ciliary smooth muscle cells increased after being treated with 0. 03% Bimatoprost. The desmosome among ciliary muscle cells decreased in number and got loose and irregular, and the collagen in extracellular matrix was decreased. Conclusion Application of 0. 03% Bimatoprost decrease the resistance of the uveoscleral outflow pathway and facilitate the aqueous fluid outflow by enhancing MMPs activity and reducing ECM components around ciliary muscle cells.