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拉帕替尼和曲妥珠单抗对实验性角膜新生血管形成中血管内皮生长因子的影响。

Effects of lapatinib and trastuzumab on vascular endothelial growth factor in experimental corneal neovascularization.

作者信息

Kaya Mehmet K, Demir Tamer, Bulut Hakan, Akpolat Nusret, Turgut Burak

机构信息

Ophthalmology Clinic, Avrupa Göz Hastanesi, Elazig, Turkey.

Department of Ophthalmology, School of Medicine, Fırat University, Elazig, Turkey.

出版信息

Clin Exp Ophthalmol. 2015 Jul;43(5):449-57. doi: 10.1111/ceo.12500. Epub 2015 Jun 24.

Abstract

BACKGROUND

The aim of this study was to compare the effects of lapatinib and trastuzumab on vascular endothelial growth factor on experimental corneal neovascularization.

METHODS

A total of 35 Wistar albino rats were randomly divided into five groups, each containing seven animals. Corneas of rats in the control group were not cauterized and did not receive any treatment. A silver nitrate pencil was applied on the right corneas of rats in the non-control groups to induce corneal neovascularization. Rats in the sham, lapatinib, trastuzumab and lapatinib +  trastuzumab groups were administered systemic saline, 50 mg/kg lapatinib once a day orally by gavage, 4 mg/kg trastuzumab once a day intraperitoneally, or 50 mg/kg lapatinib once a day orally by gavage together with 4 mg/kg trastuzumab once a day intraperitoneally, respectively, for 7 days. Rats were sacrificed on the eighth day, and corneas were excised using a 4-mm punch trephine. Vascular endothelial growth factor immunostaining in the corneal epithelial and stromal layers was evaluated. Staining intensities were determined semi-quantitatively, and corneal vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay.

RESULTS

The mean immunostaining intensities of epithelial and stromal vascular endothelial growth factor in the control group were significantly lesser than those in the sham group (P < 0.05). The mean immunostaining intensities of epithelial and stromal vascular endothelial growth factor and vascular endothelial growth factor enzyme-linked immunosorbent assay levels of corneas in all treatment groups (lapatinib, trastuzumab and lapatinib + trastuzumab groups) were lesser than those in the sham group (P < 0.05); however, it was similar to those in the control group (P > 0.05).

CONCLUSIONS

It is suggested that systemically administered lapatinib is more effective than systemically administered trastuzumab in preventing corneal neovascularization.

摘要

背景

本研究旨在比较拉帕替尼和曲妥珠单抗对实验性角膜新生血管形成中血管内皮生长因子的影响。

方法

总共35只Wistar白化大鼠被随机分为五组,每组7只动物。对照组大鼠的角膜未烧灼且未接受任何治疗。在非对照组大鼠的右眼角膜上使用硝酸银棒诱导角膜新生血管形成。假手术组、拉帕替尼组、曲妥珠单抗组和拉帕替尼+曲妥珠单抗组的大鼠分别给予全身生理盐水、每天一次口服灌胃50 mg/kg拉帕替尼、每天一次腹腔注射4 mg/kg曲妥珠单抗,或每天一次口服灌胃50 mg/kg拉帕替尼并同时每天一次腹腔注射4 mg/kg曲妥珠单抗,持续7天。在第8天处死大鼠,使用4毫米打孔环钻切除角膜。评估角膜上皮和基质层中的血管内皮生长因子免疫染色情况。对染色强度进行半定量测定,并通过酶联免疫吸附测定法测量角膜血管内皮生长因子水平。

结果

对照组上皮和基质血管内皮生长因子的平均免疫染色强度显著低于假手术组(P < 0.05)。所有治疗组(拉帕替尼组、曲妥珠单抗组和拉帕替尼+曲妥珠单抗组)角膜的上皮和基质血管内皮生长因子平均免疫染色强度以及血管内皮生长因子酶联免疫吸附测定水平均低于假手术组(P < 0.05);然而,与对照组相似(P > 0.05)。

结论

提示全身给药时,拉帕替尼在预防角膜新生血管形成方面比曲妥珠单抗更有效。

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