ZX-5及其光学异构体对兔眼血流和大鼠视网膜功能恢复的影响

目的:研究ZX-5对缺血后视网膜功能的恢复作用,并比较其光学异构体(R,R)-ZX-5和(S,S)-ZX-5对脉络膜血流及缺血后视网膜功能恢复的影响。方法:用彩色微球技术研究兔高眼压下(40mmHg)脉络膜血流的变化。用视网膜电生理仪测量b波,评价大鼠缺血后视网膜功能的恢复情况。结果:10g/L(R,R)-ZX-5滴眼液50μL能在不同时间点提高脉络膜血流(P<0.05),而(S,S)-ZX-5在相同条件下对提高脉络膜血流没有影响。ZX-5和(R,R)-ZX-5在不同时间点对视网膜缺血后功能恢复作用明显(P<0.05),(R,R)-ZX-5的作用优于ZX-5;而(S,S)-ZX-5对缺血后视网膜功能的恢复作用不明显。结论:ZX-5和(R,R)-ZX-5对增加脉络膜血流量和促进视网膜功能的恢复有显著功效,(R,R)-ZX-5恢复视网膜功能的作用更强,有可能进一步开发成有效防治眼血流障碍相关性眼病的药物。

Effects of ZX-5 and its optical isomers on ocular blood flow in rabbits and retinal function recovery in rats

AIM: The effects of ZX-5, as nitric oxide (NO) donor, on ocular blood flow has been investigated using colored microsphere technique in previous study. The relationship between the production of NO by ZX-5 and ocular blood flow has been evaluated. ZX-5 has been shown to have strong positive effect on increasing choroidal blood flow. However,the effect of ZX-5 on retinal function recovery, the effects of its optical isomers, (R, R)-ZX-5 and (S, S)-ZX-5, on choroidal blood flow and retinal function recovery have not been studied and merit investigation.METHODS: Colored microsphere technique was used for in vivo experiments to determine choroidal blood flow of ocular hypertension (40mmHg) in rabbit eyes. Electroretinography was used to measure the b-wave recovery as an indication of retinal function recovery.RESULTS: (R, R)-ZX-5 increased choroidal blood flow at 10g/L, 50μL instillation into eyes at all time points (P＜0.05).(S, S)-ZX-5 was not effective in increasing choroidal blood flow. ZX-5 and (R, R)-ZX-5 showed significant effects in retinal function recovery after ischemia of the retina at all time points (P＜0.05); whereas (S, S)-ZX-5 did not show significant effect on recovery of b-wave after ischemia at most time points except at 120 and 240 minutes.CONCLUSION: ZX-5 and (R, R)-ZX-5 have high potency in increasing the choroidal blood flow and improving the retinal function recovery. It is hoped that they could be used for the prevention/treatment of ocular blood flow related eye diseases.