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组蛋白去乙酰化酶抑制剂丁酰氧甲基二乙基磷酸酯(AN-7)对小鼠模型角膜新生血管形成的影响

Effect of Histone Deacetylase Inhibitor, Butyroyloxymethyl-Diethyl Phosphate (AN-7), on Corneal Neovascularization in a Mouse Model.

作者信息

Schaap-Fogler Michal, Bahar Irit, Rephaeli Ada, Dahbash Mor, Nudelman Abraham, Livny Eitan, Barliya Tilda, Nisgav Yael, Livnat Tami

机构信息

1 Department of Ophthalmology, Rabin Medical Center , Petah Tikva, Israel .

2 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .

出版信息

J Ocul Pharmacol Ther. 2017 Jul/Aug;33(6):480-486. doi: 10.1089/jop.2016.0017. Epub 2017 Mar 24.

Abstract

PURPOSE

To examine whether butyroyloxymethyl-diethyl phosphate (AN-7), a histone deacetylase inhibitor, inhibits chemically induced corneal neovascularization (NV) in mice.

METHODS

Corneal NV was induced in the right eye of male C57BL mice by application of a mixture of 75% silver nitrate and 25% potassium nitrate to the corneal center. Immediately thereafter, the mice were randomized into 2 groups, receiving an intraperitoneal injection of AN-7 or saline, which served as control. Corneal NV was evaluated at constant time intervals from the corneal injury by corneal photographs and the area of corneal NV was measured. Centricity and density of the corneal vascularization were graded. Corneal flat mounts blood vessels staining and histological studies were performed on day 10. Unpaired t-test was used for group comparisons.

RESULTS

The corneal neovascular area was statistically significantly reduced by AN-7 treatment on days 10 and 14 postinjury and compared with the untreated group. The centricity and density of the corneal NV between treated and untreated groups showed no significant difference at any time point.

CONCLUSIONS

Systemic treatment with AN-7 had a significant inhibitory effect on chemical burn-induced corneal NV in mice. These results suggest that AN-7 should be further evaluated for its therapeutic potential for the treatment of corneal NV.

摘要

目的

研究组蛋白脱乙酰酶抑制剂丁酰氧基甲基二乙基磷酸酯(AN-7)是否能抑制化学诱导的小鼠角膜新生血管形成(NV)。

方法

通过向雄性C57BL小鼠右眼角膜中心涂抹75%硝酸银和25%硝酸钾的混合物诱导角膜NV。此后立即将小鼠随机分为2组,分别腹腔注射AN-7或生理盐水作为对照。通过角膜照片在固定时间间隔评估角膜NV,并测量角膜NV的面积。对角膜血管化的中心性和密度进行分级。在第10天进行角膜平铺血管染色和组织学研究。采用非配对t检验进行组间比较。

结果

与未治疗组相比,AN-7治疗在损伤后第10天和第14天使角膜新生血管面积有统计学意义的显著减少。治疗组和未治疗组之间角膜NV的中心性和密度在任何时间点均无显著差异。

结论

AN-7全身治疗对化学烧伤诱导的小鼠角膜NV有显著抑制作用。这些结果表明,应进一步评估AN-7治疗角膜NV的治疗潜力。

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