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通过针对 VEGF 和 HIF-1α 的双靶点干扰抑制兔角膜碱烧伤后的角膜新生血管形成。

Inhibited corneal neovascularization in rabbits following corneal alkali burn by double-target interference for VEGF and HIF-1α.

机构信息

Department of Burns and Plastic Surgery, Shengli Oilfield Central Hospital, Dongying 257034, P.R. China

Department of Burns and Plastic Surgery, Shengli Oilfield Central Hospital, Dongying 257034, P.R. China.

出版信息

Biosci Rep. 2019 Jan 30;39(1). doi: 10.1042/BSR20180552. Print 2019 Jan 31.

Abstract

Expression of hypoxia-inducible factor (HIF) 1α has been observed in corneal neovascularization (CNV). Vascular endothelial growth factor (VEGF), one of the most well-known angiogenic factors in CNV, is under the regulation of HIF-1. The present study aims to investigate the synergistic effects of VEGF and HIF-1α gene silencing on alkali burn-induced CNV in rabbits. The models of rabbits in corneal alkali burn were established. SiRNA recombinant adenovirus was used to explore the synergistic effects of VEGF and HIF-1α gene silencing on alkali burn-induced CNV. CNV area and ultrastructure of cornea were observed. The expression of VEGF and HIF-1α was detected. CNV was observed in rabbits following alkali burn. In addition, overexpressed VEGF and HIF-1α was also observed in rabbits following alkali burn. Then, silencing HIF-1α or silencing VEGF decreased area of CNV, inhibited neovascularization and improved pathological changes, while double-target interference for VEGF and HIF-1α decreased area of CNV inhibited neovascularization, and improved pathological changes to a greater extent. Our study provides evidences emphasizing the distinct notion that VEGF and HIF-1α play the contributory role in alkali burn-induced CNV as a result of double-target interference for VEGF and HIF-1α inhibiting CNV in rabbits following corneal alkali burn.

摘要

缺氧诱导因子 (HIF) 1α 的表达已在角膜新生血管化 (CNV) 中观察到。血管内皮生长因子 (VEGF) 是 CNV 中最著名的血管生成因子之一,受 HIF-1 调节。本研究旨在探讨 VEGF 和 HIF-1α 基因沉默对兔碱性烧伤诱导的 CNV 的协同作用。建立兔角膜碱烧伤模型。使用 siRNA 重组腺病毒探讨 VEGF 和 HIF-1α 基因沉默对碱性烧伤诱导的 CNV 的协同作用。观察 CNV 面积和角膜超微结构。检测 VEGF 和 HIF-1α 的表达。兔角膜碱烧伤后观察到 CNV。此外,兔角膜碱烧伤后还观察到 VEGF 和 HIF-1α 的过表达。然后,沉默 HIF-1α 或沉默 VEGF 可减少 CNV 面积,抑制新生血管形成并改善病理变化,而 VEGF 和 HIF-1α 的双重靶向干扰可进一步减少 CNV 面积,抑制新生血管形成,并改善病理变化。我们的研究提供了证据,强调了 VEGF 和 HIF-1α 通过 VEGF 和 HIF-1α 的双重靶向干扰在兔角膜碱烧伤后抑制 CNV 中,作为导致碱烧伤诱导的 CNV 的协同作用的明显概念。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bbb/6356011/315b567476a2/bsr-39-bsr20180552-g1.jpg

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