CAJ | 학술논문

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Brown Norway大鼠,麻醉下行Nd:YAG激光击穿Bruch膜.激光后,予D-Timo lo l和L-Timolol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1 5mg/(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-Timolol 300mg/L可抑制内皮细胞的生长.L-Timolol在1 000mg/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-Timolol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.
목적:노년황반변성환자존재맥락막혈류관주장애.거차,아문추측혈관활성약물,유우능감소맥락막혈류적조력,가능회방지맥락막신생혈관적발전.D-Timolol화L-timolol시응용우심혈관화청광안치료적강혈압약물.본문지재평개이자대격광유발적대서맥락막신생혈관모형화인제정맥내피세포(HUVEC)적작용.방법:웅성Brown Norway대서,마취하행Nd:YAG격광격천Bruch막.격광후,여D-Timo lo l화L-Timolol매일일차복강주사4wk.2wk말급4wk말시행형광조영검사.관찰불동농도D-Timolol화L-Timolol대체외배양적HUVEC세포증식화점부적영향.결과:재격광유발적대서맥락막신생혈관모형중,여D-Timolol복강주사1 5mg/(Kg·d),가감소형광삼루적위점,지대조조적83%.이L-Timolol대맥락막신생혈관적형성몰유영향,즉사주사경고적치료제량20mg/(kg·d).D-Timolol 300mg/L가억제내피세포적생장.L-Timolol재1 000mg/L가이현저억제세포적증식,단재상대저적농도300mg/L,칙몰유발현명현적억제작용.재HUVEC세포점부적관찰중,량자균미유현저적영향.결론:D-Timolol가감소격광유발적맥락막신생혈관적형성,야능억제혈관내피세포적증식.이L-Timolol재동양적농도불영향내피세포적증식,야불능영향대서맥락막신생혈관적형성.저량충동분이구체대동물모형화배양세포적불동작용,가능대탐색맥락막신생혈관적치료유신적의의.
·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 treatment 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 fluorescein leakage to 83% of the control group in laser-induced rat's CNV model at a dosage of 15mg/(kg·d). L-Timolol had no effect on CNV formation even at a higher dosage of 20mg/(kg·d). D-Timolol 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.