D-Timolol和L-Timolol对大鼠脉络膜新生血管及内皮细胞的作用(英文)  

The effect of D-Timolol and L-Timolol on rat experimental choroidal neovascularization in vivo and endothelial cells in vitro

作　　者：徐新荣 邹燕红 邱春亿 

机构地区：[1]美国德克萨斯A&M大学医学院医学药理与毒理系

出　　处：《国际眼科杂志》2005年第5期831-835,共5页International Eye Science

摘　　要：目的:老年黄斑变性患者存在脉络膜血流灌注障碍。据此,我们推测血管活性药物,由于能减小脉络膜血流的阻力,可能会防止脉络膜新生血管的发展。D-Timolol和L-timolol是应用于心血管和青光眼治疗的降血压药物。本文旨在评价二者对激光诱发的大鼠脉络膜新生血管模型和人脐静脉内皮细胞(HUVEC)的作用。方法:雄性BrownNorway大鼠,麻醉下行Nd:YAG激光击穿Bruch膜。激光后,予D-Timolol和L-Tim-olol每日一次腹腔注射4wk。2wk末及4wk末时行荧光造影检查。观察不同浓度D-Timolol和L-Timolol对体外培养的HUVEC细胞增殖和黏附的影响。结果:在激光诱发的大鼠脉络膜新生血管模型中,予D-Timolol腹腔注射15mg/(Kg·d),可减少荧光渗漏的位点,至对照组的83%。而L-Timolol对脉络膜新生血管的形成没有影响,即使注射更高的治疗剂量20mg/(kg·d)。D-Timolol300mg/L可抑制内皮细胞的生长。L-Timolol在1000mg/L可以显著抑制细胞的增殖,但在相对低的浓度300mg/L,则没有发现明显的抑制作用。在HUVEC细胞黏附的观察中,两者均未有显著的影响。结论:D-Timolol可减少激光诱发的脉络膜新生血管的形成,也能抑制血管内皮细胞的增殖。而L-Tim-olol在同样的浓度不影响内皮细胞的增殖,也不能影响大鼠脉络膜新生血管的形成。这两种同分异构体对动物模型和培养细胞的不同作用,可能对探索脉络膜新生血管的治疗有新的意义。AIM： Impairment of choroidal perfusion was found in AMD patients. We postulated that vasoactive agents, which can reduce choroidal blood flow resistance, might prevent the development of choroidal neovascularization （CNV）. D-Timolol and L-Timolol are hypotensive agents used in cardiovascular and glaucoma therapy. Their effects on laser-induced experimental CNV rat model and human umbilical vein endothelial cells （HUVEC） were thus evaluated. METHODS： Male Brown Norway rats were anesthetized to receive Nd：YAG laser to break the Bruch＇s membrane. D-Timolol and L-Timolol were given once daily through intraperitoneal injection after laser treat- ment for 4wk. Fluorescein angiography was performed on 2wk and 4wk. HUVEC were tested by proliferation assay and adhesion assay with D-Timolol and L-Timolol at different concentrations.RESULTS： D-Timolol reduced the fiuorescein leakage to 83% of the control group in laser-induced rat＇s CNV model at a dosage of 15mg/（kgod）. L-Timolol had no effect on CNV formation even at a higher dosage of 20mg/ （kgod）. D-Tomolol inhibited the endothelial cells proliferation significantly by 300mg/L. L-Timolol also significantly inhibited the cell proliferation at 1 000mg/L. But at a lower dose such as 300mg/L, no significant inhibitory effect was found. Both drugs showed no effect on cell adhesion function in cell culture experiments. CONCLUSION： D-Timolol was found to prevent CNV development in laser-induced model in vivo and inhibit vascular endothelial cells proliferation in vitro. L-Timolol had no effect on cell proliferation at the same dose, and neither on rat CNV model. The results indicate these two isomers have different functions on rat＇s CNV prevention and on HUVEC cell proliferation.

关 键 词：D-Timolol L-Timolol 脉络膜新生血管 大鼠 脉络膜新生血管模型 人脐静脉内皮细胞 ND:YAG激光 TIMOLOL 脉络膜血流 青光眼治疗 

分 类 号：R774.5[医药卫生—眼科]