熊去氧胆酸和牛磺熊去氧胆酸抑制激光处理大鼠模型中的脉络膜新生血管。

Ursodeoxycholic acid and tauroursodeoxycholic acid suppress choroidal neovascularization in a laser-treated rat model.

机构信息

Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, Korea.

出版信息

J Ocul Pharmacol Ther. 2010 Jun;26(3):223-9. doi: 10.1089/jop.2010.0012.

DOI:10.1089/jop.2010.0012

PMID:20565307

Abstract

PURPOSE

The aim of this study was to investigate the suppressing effects of systemically administered ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) on choroidal neovascularization (CNV) in a laser-treated rat model.

METHODS

CNV was induced by argon laser photocoagulation in the right eye of each animal. UDCA 500 mg/kg, TUDCA 100 mg/kg, or vehicle was intraperitoneally injected at 24 h before and daily after laser treatment. Fourteen days after laser treatment, fluorescein angiography was performed to evaluate leakage from CNV and eyes were enucleated for histologic evaluation. Vascular endothelial growth factor (VEGF) levels in the retina were measured using enzyme-linked immunosorbent assay at 3 days after laser treatment and were compared between the UDCA, TUDCA, and control groups.

RESULTS

The proportion of CNV lesions showing clinically significant fluorescein leakage was lower in the UDCA and TUDCA groups (42%, P = 0.0124; and 46%, P = 0.0292) than in the control group (67%). CNV lesion dimensions including CNV area and CNV/choroid thickness ratio were also significantly reduced in the UDCA and TUDCA groups (7,664 +/- 630 microm(2), P < 0.001 and 8,558 +/- 570 microm(2), P < 0.001; 2.35 +/- 0.16, P = 0.026 and 2.27 +/- 0.15, P = 0.003) compared with the control group (12,147 +/- 661 microm(2) and 3.10 +/- 0.27). The VEGF level in the retina after laser treatment was lower in the TUDCA group than that in the control group (9.0 +/- 2.7 pg/mg vs. 29.4 +/- 8.2 pg/mg, P = 0.032), whereas the UDCA group showed no difference.

CONCLUSIONS

The systemic administration of UDCA and TUDCA suppressed laser-induced CNV formation in rats, which might be associated with anti-inflammatory action. The result indicates that UDCA and TUDCA are potential candidate drugs for the treatment of many CNV-related retinal diseases, including age-related macular degeneration.

摘要

目的

本研究旨在探讨熊去氧胆酸（UDCA）和牛磺熊去氧胆酸（TUDCA）全身给药对激光诱导的大鼠脉络膜新生血管（CNV）的抑制作用。

方法

在每只动物的右眼通过氩激光光凝诱导 CNV。在激光治疗前 24 小时和每日一次腹腔内注射 UDCA 500mg/kg、TUDCA 100mg/kg 或载体。激光治疗后 14 天，行荧光素血管造影评估 CNV 渗漏，并眼球摘出进行组织学评估。在激光治疗后 3 天，采用酶联免疫吸附试验测量视网膜中血管内皮生长因子（VEGF）水平，并在 UDCA、TUDCA 和对照组之间进行比较。

结果

UDCA 和 TUDCA 组（42%，P=0.0124；46%，P=0.0292）中显示临床显著荧光素渗漏的 CNV 病变比例低于对照组（67%）。UDCA 和 TUDCA 组的 CNV 病变尺寸（包括 CNV 面积和 CNV/脉络膜厚度比）也显著减小（7664±630μm2，P<0.001 和 8558±570μm2，P<0.001；2.35±0.16，P=0.026 和 2.27±0.15，P=0.003），与对照组（12147±661μm2和 3.10±0.27）相比。激光治疗后视网膜中的 VEGF 水平在 TUDCA 组低于对照组（9.0±2.7pg/mg 比 29.4±8.2pg/mg，P=0.032），而 UDCA 组则无差异。