论文部分内容阅读
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。
OBJECTIVE: Choroidal blood flow disorders are present in patients with age-related macular degeneration. Accordingly, we hypothesize that vasoactive drugs may prevent the development of choroidal neovascularization by reducing the resistance to choroidal blood flow. D-Timolol and L-timolol are hypotensive drugs used in the treatment of cardiovascular and glaucoma. This article aims to evaluate the effects of both on the choroidal neovascularization and human umbilical vein endothelial cells (HUVECs) induced by laser in rats. METHODS: Male Brown Norway rats were anesthetized with Nd: YAG laser to penetrate Bruch’s membrane. After laser, D-Timolol and L-Tim-olol were intraperitoneally injected for 4 weeks. 2wk and 4wk at the end of time fluorescence imaging. To observe the effect of different concentrations of D-Timolol and L-Timolol on the proliferation and adhesion of HUVEC cultured in vitro. RESULTS: Intraperitoneal injection of 15 mg / (Kg · d) D-Timolol in the laser-induced rat choroidal neovascularization model reduced the site of fluorescence leakage to 83% of the control group. However, L-Timolol had no effect on the formation of choroidal neovascularization, even at a higher therapeutic dose of 20 mg / (kg · d). D-Timolol 300mg / L can inhibit the growth of endothelial cells. L-Timolol at 1000mg / L can significantly inhibit cell proliferation, but at a relatively low concentration of 300mg / L, no significant inhibition was found. In the observation of HUVEC cell adhesion, both had no significant effect. Conclusion: D-Timolol can reduce the laser-induced formation of choroidal neovascularization and also inhibit the proliferation of vascular endothelial cells. However, L-Tim-olol did not affect the proliferation of endothelial cells at the same concentration, nor did it affect the formation of rat choroidal neovascularization. The different effects of these two isomers on animal models and cultured cells may have new implications for the exploration of choroidal neovascularization.