胼酞嗪对眼血流和激光诱导的脉络膜新生血管及体外培养的内皮细胞的影响(英文)

Effects of hydralazine on ocular blood flow and laser-induced choroidal neovascularization

目的:研究胼酞嗪对兔脉络膜血流和激光诱导的鼠脉络膜新生血管及人脐静脉内皮细胞管状结构形成的影响。方法:雌性新西兰白兔左眼眼内压升高至40mmHg后,滴入10g/L胼酞嗪滴眼液,采用彩色微球技术测量眼血流变化。用Nd:YAG激光诱导雄性Brown Norway大鼠至Bruch膜破裂,而后分别予生理盐水或5,10和20g/L胼酞嗪滴眼液点眼,3次/d,连续4wk。采用眼底荧光血管造影和脉络膜平片测量新生血管的面积。此外亦用不同浓度的胼酞嗪作用于培养之人脐静脉内皮细胞并探讨对其管状结构形成的影响。结果:10g/L胼酞嗪滴眼液滴入眼内压为40mmHg的兔眼30,60min后,脉络膜血流明显增加。眼底荧光血管造影和脉络膜平片测量均显示,经过4wk药物治疗,5,10,20g/L胼酞嗪滴眼液均明显抑制了鼠眼CNV的形成。3～30mg/L胼酞嗪对在基质凝胶中培养了48h的人脐静脉内皮细胞的管状结构的形成有抑制作用。结论:胼酞嗪可以抑制体内脉络膜新生血管及体外培养的人脐静脉内皮细胞管状结构的形成,并增强缺血后的兔脉络膜血流。胼酞嗪有望成为治疗年龄相关性黄斑变性的药物。

AIM： To investigate the effect of hydralazine on choroidal blood flow in rabbits and laser-induced choroidal neovascularization （CNV） in rats and the effect of hydralazine on tube formation of human umbilical vein endothelial cells （HUVEC）. METHODS： Female New Zealand white rabbits were used with raised intraoculsr pressure （IOP） of the left eye to 40mmHg. Hydralazine （10g/L） eye drops were instilled and ocular blood flow was measured with colored microspheres technique. Male Brown Norway rats were treated with Nd： YAG laser to break Bruch＇s membrane. Hydralazine （5,10, 20g/L） eye drops or saline alone was instilled three times a day for 4 weeks after laser treatment. Fluorescein angiography （FA） and choroidal flat mount were used to measure the area of CNV. Tube formation of HUVEC was studied at different concentrations of hydralazine. RESULTS： With raised lOP to 40mmHg on rabbits, 10g/L hydralazine eye drops enhanced the choroidal blood flow significantly at 30 and 60 minutes after drug instillation. After 4 week of drug treatment, 5, 10 and 20g/L hydralazine eye drops all reduced the CNV formation dramatically measured by fluorescein angiography and choroidal flat mount. When HUVEC was cultured on matrix gel for 48 hours, hydralazine at 3-30mg/L prevented the tube formation. CONCLUSION ： Hydralazine prevented CNV formation in vivo and HUVEC tube formation in vitro, and enhanced rabbits＇ choroidal blood flow after ischemia. It is hoped that hydralazine could be used to treat age-related macular degeneration in the future.