The effect of hypoxia-inducible factor-2α expressing in the neovascularization of the proliferative diabetic retinopathy

Q4 Medicine

中华眼底病杂志 Pub Date : 2020-02-25 DOI:10.3760/CMA.J.ISSN.1005-1015.2020.02.005

Qing-bao Guo, Xuxia Meng, Die Hu, Xianhui Zhou, Chuan Yu

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Abstract

Objective To observe and investigate the effect of HIF-2α in the process of neovascularization of proliferative diabetic retinopathy (PDR). Methods Retrospective clinical study. From July 2014 to July 2015, 60 eyes of 57 PDR patients diagnosed in Ophthalmology Department of Affiliated Hospital of Qingdao University were included in the study. Twenty-eight eyes of 27 patients received intravitreal injections of 0.5 mg ranibizumab (0.05 ml) at 2-7 days before surgery (ranibizumab group) and other 32 eyes of 30 patients did not (group without ranibizumab). Eighteen eyes of 18 patients with epiretinal membranes were included as controls. Pathological specimens of PDR fibrovascular membrane and premacular membrane were obtained during vitrectomy. The immunohistochemical staining and real-time PCR (RT-PCR) were used to detecting the expression of HIF-2α, Dll4 and VEGF. Kruskal-wallis test was used to compare the expression differences of correlation factors between groups. Spearman correlation analysis was used to analyze the relationship between the two variables. Results The immunohistochemical staining revealed that there were positive expression of HIF-2α, Dll4 and VEGF in all PDR membranes, regardless of the injection of the ranibizumab. The levels of HIF-2α, Dll4 and VEGF protein in the group without ranibizumab were higher than those of the ranibizumab group (t=4.36, 6.01, 4.82; P=0.000, 0.008, 0.016). RT-PCR showed that the differences of the mRNA expression of HIF-2α, Dll4 and VEGF were all statistically significant among the PDR patients and controls (H=18.81,19.60, 20.50; P=0.000, 0.000, 0.000). The expression of HIF-2α, Dll4 and VEGF in the PDR membranes was higher than that of epiretinal membranes from non-diabetic patients. In the PDR patients,the expression of HIF-2α, Dll4 and VEGF of the group without ranibizumab was higher than that of the ranibizumab group. The spearman correlation analysis showed that the expression of mRNA between HIF-2α and Dll4, HIF-2α and VEGF were both significantly correlated (r=0.95, 0.87; P<0.05). Conclusions The expression of HIF-2α in the PDR membranes was higher than that of the controls. It is positively correlated with the expression of the DLL4 and VEGF. Key words: Diabetic retinopathy; Retinal neovascularization; Hypoxia-inducible factor 1

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缺氧诱导因子-2α表达在增生性糖尿病视网膜病变新生血管中的作用

目的观察和探讨HIF-1α在增殖性糖尿病视网膜病变（PDR）新生血管形成过程中的作用。方法回顾性临床研究。2014年7月至2015年7月，在青岛大学附属医院眼科诊断的57例PDR患者的60只眼纳入本研究。27名患者中的28只眼睛在手术前2-7天接受了0.5 mg雷尼珠单抗（0.05 ml）的玻璃体内注射（雷尼珠珠单抗组），30名患者中其他32只眼睛没有接受（没有雷尼珠mab的组）。18例视网膜前膜患者的18只眼睛作为对照。玻璃体切除术中获得PDR纤维血管膜和眼前膜的病理标本。免疫组织化学染色和实时聚合酶链式反应（RT-PCR）检测HIF-1α、Dll4和VEGF的表达。Kruskal-wallis检验用于比较各组之间相关因素的表达差异。Spearman相关分析用于分析两个变量之间的关系。结果免疫组化染色显示，在所有PDR膜中，HIF-1α、Dll4和VEGF均呈阳性表达。未使用雷尼珠单抗组的HIF-2α、Dll4和VEGF蛋白水平高于使用雷尼单抗组（t=4.36,6014.82；P=0.0001.008,0.016），PDR膜中的Dll4和VEGF高于非糖尿病患者的视网膜前膜。在PDR患者中，不使用雷尼珠单抗组的HIF-1α、Dll4和VEGF的表达高于使用雷尼单抗组。spearman相关性分析显示，HIF-1α与Dll4、HIF-1α和VEGF的mRNA表达均呈显著相关（r=0.95，0.87；P<0.05）。它与DLL4和VEGF的表达呈正相关。关键词：糖尿病视网膜病变；视网膜新生血管；缺氧诱导因子1

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来源期刊

中华眼底病杂志 Medicine-Ophthalmology

CiteScore

0.40

自引率

0.00%

发文量

5383

期刊介绍： Chinese Journal of Ocular Fundus Diseases is the only scientific journal in my country that focuses on reporting fundus diseases. Its purpose is to combine clinical and basic research, and to give equal importance to improvement and popularization. It comprehensively reflects the leading clinical and basic research results of fundus disease disciplines in my country; cultivates professional talents in fundus disease, promotes the development of fundus disease disciplines in my country; and promotes academic exchanges on fundus disease at home and abroad. The coverage includes clinical and basic research results of posterior segment diseases such as retina, uveal tract, vitreous body, visual pathway, and internal eye diseases related to systemic diseases. The readers are medical workers and researchers related to clinical and basic research of fundus diseases. According to the journal retrieval report of the Chinese Institute of Scientific and Technological Information, the comprehensive ranking impact factor and total citation frequency of the Chinese Journal of Ocular Fundus Diseases have been among the best in the disciplines of ophthalmology, otolaryngology, and ophthalmology in my country for many years. The papers published have been included in many important databases at home and abroad, such as Scopus, Peking University Core, and China Science Citation Database (CSCD).