多西环素对眼部血管生成的影响：体内分析。
Doxycycline's effect on ocular angiogenesis: an in vivo analysis.
机构信息
National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
出版信息
Ophthalmology. 2010 Sep;117(9):1782-91. doi: 10.1016/j.ophtha.2010.01.037. Epub 2010 Jun 3.
PURPOSE
To determine the in vivo effect of doxycycline on choroidal angiogenesis and pterygium growth by using a choroidal neovascular (CNV) murine model, a directed in vivo angiogenesis assay (DIVAA) and a pterygium murine model.
DESIGN
Experimental study.
PARTICIPANTS
Three murine models were investigated with 4 mice minimum per group and 22 maximum per group.
METHODS
Mice received water with or without doxycycline. For the CNV, the neovascular lesion volume was determined in choroid-retinal pigment epithelial flat mounts using confocal microscopy 7 days after laser induction. For DIVAA, silicone capsules containing 10,000 human pterygium epithelial cells were implanted in the flanks of mice subcutaneously. After 11 days, neovascularization (NV) was quantified using spectrofluorometry after murine tail-vein injection of fluorescein isothiocyanate-labeled dextran. A pterygium epithelial cell model was developed by injecting 10,000 human pterygium epithelial cells in the nasal subconjunctival space in athymic nude mice. Doxycycline was started on day 6 at 50 mg/kg per day; corneal lesions that resulted from the injections were compared at days 6 and 15.
MAIN OUTCOME MEASURES
The Student t-test was used to evaluate the data for the CNV and DIVAA models and histologic preparations were used to evaluate pterygia lesions.
RESULTS
There was significantly less NV and lesion volume with doxycycline taken in drinking water versus plain water. With doxycycline treatment, the laser-induced CNV showed a maximal 66% decrease in choroidal blood vessel volume (P< or =0.008) and the DIVAA showed a 30% reduction of blood vessel growth and migration (P<0.004). Histologic preparations demonstrated that pterygium cell lesions regressed when mice were administered doxycycline for 9 days.
CONCLUSIONS
Doxycycline significantly inhibited angiogenesis in 3 murine models. The most dramatic effect was found in the CNV model followed by the pterygia epithelial cell DIVAA model. The anterior segment pterygium model also showed regression histologically. This suggests that doxycycline may be successful as an adjunctive treatment for CNV and pterygia in humans; clinical trials would be necessary to determine if there is a benefit.
目的
通过脉络膜新生血管（CNV）鼠模型、定向活体血管生成分析（DIVAA）和翼状胬肉鼠模型，确定强力霉素对脉络膜血管生成和翼状胬肉生长的体内作用。
设计
实验研究。
参与者
每组至少 4 只，最多 22 只小鼠，共 3 个鼠模型。
方法
小鼠饮用含或不含强力霉素的水。CNV 模型中，激光诱导后第 7 天，通过共聚焦显微镜确定脉络膜-视网膜色素上皮平面的新生血管病变体积。DIVAA 中，将含有 10000 个人翼状胬肉上皮细胞的硅胶囊皮下植入小鼠的侧腹。11 天后，通过尾静脉注射异硫氰酸荧光素标记的葡聚糖，使用分光荧光法定量血管生成（NV）。在无胸腺裸鼠的鼻结膜下空间注射 10000 个人翼状胬肉上皮细胞，建立翼状胬肉上皮细胞模型。第 6 天开始，每天 50mg/kg 强力霉素，比较第 6 天和第 15 天的角膜病变。
主要观察指标
CNV 和 DIVAA 模型采用 Student t 检验评估数据，组织学切片评估翼状胬肉病变。
结果
与普通水相比，饮用水中强力霉素的 NV 和病变体积明显减少。强力霉素治疗后，激光诱导的 CNV 脉络膜血管体积最大减少 66%（P<0.008），DIVAA 显示血管生长和迁移减少 30%（P<0.004）。组织学切片显示，当小鼠连续 9 天给予强力霉素时，翼状胬肉细胞病变消退。
结论
强力霉素显著抑制了 3 种鼠模型中的血管生成。CNV 模型中效果最显著，其次是翼状胬肉上皮细胞 DIVAA 模型。前节翼状胬肉模型在组织学上也有消退。这表明强力霉素可能成为治疗 CNV 和人翼状胬肉的辅助治疗方法；需要进行临床试验以确定是否有获益。
Zotero 插件