缺氧诱导因子1α在碱烧伤后兔角膜新生血管形成中的作用

目的 观察碱烧伤后兔角膜新生血管形成的不同时期缺氧诱导因子1α(HIF-1α)在角膜内的表达,探讨HIF-1α对角膜新生血管形成的影响.方法 实验研究.取30只健康家兔,采用随机数字表法分成5组,每组各6只兔,右眼采用1 mol/L氢氧化钠溶液建立角膜碱烧伤模型,左眼作为自身对照.分别于碱烧伤前和碱烧伤后1、3、5、7、14 d,在裂隙灯显微镜下观察家兔角膜新生血管增生情况,HE染色观察角膜组织病理学特征,并采用免疫组织化学法检验角膜组织中HIF-1α的表达,计算炎性细胞(多形核白细胞和淋巴细胞)和HIF-1α阳性细胞核数,对其结果行单因素方差分析及相关分析.结果 角膜碱烧伤后,HIF-1α主要表达在角膜基质中的炎性细胞、血管内皮细胞的细胞核中.随着时间的增加,炎性细胞表达增强,HIF-1α表达量也相应增加,并于碱烧伤后5 d达到高峰,以后逐渐减少.碱烧伤后1、3、5、7、14 d,角膜组织中炎性细胞和HIF-1α表达水平的差异均有统计学意义(F=422.086,437.555;P均＜0.05),且HIF-1α的表达与新生血管的形成在时空上一致.经相关分析,角膜中炎性细胞和HIF-1α阳性细胞表达呈正相关(r=0.860,P＜0.05).结论 碱烧伤后炎症反应能诱导HIF-1α的表达,而HIF-1α能促进角膜新生血管的形成.

Role of hypoxia-inducible factor 1α on corneal neovascularization after alkali burn in rabbits

Objective To observe the expression of hypoxia-inducible factor 1α(HIF-1α) on corneal neovascularization at different periods after alkali burn in rabbits, and to investigate the effect of HIF-1α on corneal neovascularization. Methods Experimental study. One mol/L NaOH was used to establish a corneal alkali burn model on the right eyes of 30 healthy rabbits (left eyes were the controls). The rabbits were randomly divided into 5 groups, 6 rabbits in each group. Corneal neovascularization (CNV) of rabbit morphology with HE staining was observed before alkali burn and 1, 3, 5, 7, and 14 days after burn. Meanwhile, the expression of inflammatory cells (polymorphonuclear leukocyte and lymphocyte) and HIF-1α on corneal tissues was tested with an immunohistochemical method and quantified by counting the positive nuclei, and analyzed with a One-Way analysis of variance and correlation analysis. Results The protein of HIF-1α was expressed in inflammatory cells and neovascular endothelial cells of corneal stroma. The expression of HIF-1α gradually increased with the expression of inflammatory cells, peaked on the 5th day, then decreased with time. Inflammatory cells and HIF-1α levels in each group at 1, 3, 5, 7, and 14days after alkali burn were statistically different (F=422.286, 437.555; P＜0.05 for both). Positive correlations were found between inflammatory cells and HIF-1α positive cells by correlation analysis (r=0.860, P＜0.05). The expression of HIF-1α was parallel to the formtion of new blood vessels in the cornea. Conclusion Inflammation can induce the expression of HIF-1α after alkali burn. The expression of HIF-Iα can promote the corneal neovascularization.