缺氧诱导因子-2α在增生型糖尿病视网膜病变新生血管形成中的作用  

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

作　　者：郭庆敏[1,2] 孟旭霞 胡迭[1,3] 周贤慧 余川[1,5] Guo Qingmin;Meng Xuxia;Hu Die;Zhou Xianhui;Yu Chuan(Department of Ophthalmology,Affiliated Hospital of Qingdao University,Qingdao 266500,China;Hebei Eye Hospital,Xingtai 054001,China;Qingdao Eye Hospital,Qingdao 266071,China;Department of Ophthalmology,Yantai YeDa Hospital,Yantai 264006,China;Wuhan Aige Eye Hospital,Wuhan 430015,China)

机构地区：[1]青岛大学附属医院眼科,266500 [2]河北省眼科医院,邢台054001 [3]青岛眼科医院,266071 [4]在烟台业达医院眼科,264006 [5]武汉艾格眼科医院,430015

出　　处：《中华眼底病杂志》2020年第2期110-115,共6页Chinese Journal of Ocular Fundus Diseases

摘　　要：目的观察HIF-2α在增生型糖尿病视网膜病变(PDR)纤维血管膜中的表达,初步探讨HIF-2α在PDR新生血管形成中的作用。方法回顾性临床研究。2014年7月至2015年7月于青岛大学附属医院眼科行玻璃体切割手术的PDR患者57例60只眼纳入研究。根据手术前是否行玻璃体腔注射抗VEGF药物治疗将患眼分为PDR未注药组和PDR注药组,分别为30例32只眼、27例28只眼。PDR注药组患眼手术前2~7 d玻璃体腔注射10 mg/ml雷珠单抗0.05 ml(含雷珠单抗0.5 mg)。选取同期特发性黄斑前膜患者18例18只眼作为对照组。于玻璃体切割手术中获得PDR纤维血管膜、黄斑前膜病理标本。免疫组织化学染色法及荧光定量PCR(RT-PCR)检测各组病理标本中HIF-2α、Delta样配体4(Dll4)、VEGF的表达。多组间相关因子表达差异比较采用Kruskal-Wallis检验。两变量间关系行Spearman相关性分析。结果免疫组织化学染色结果显示,PDR未注药组、PDR注药组纤维血管膜中HIF-2α、Dll4、VEGF蛋白表达均呈阳性。PDR未注药组HIF-2α、Dll4、VEGF蛋白相对表达量均高于PDR注药组,差异均有统计学意义(t=4.36、6.01、4.82,P=0.000、0.008、0.016)。RT-PCR检测结果显示,PDR未注药组、PDR注药组、对照组纤维血管膜、黄斑前膜中HIF-2α、Dll4、VEGF mRNA相对表达量比较,差异均有统计学意义(H=18.81、19.60、20.50,P=0.000、0.000、0.000)。其中,PDR未注药组、PDR注药组HIF-2α、Dll4、VEGF mRNA相对表达量均显著高于对照组;与PDR未注药组比较,PDR注药组HIF-2α、Dll4、VEGF mRNA相对表达量均降低。Spearman相关性分析结果显示,HIF-2α与Dll4、VEGF mRNA相对表达量呈显著正相关(r=0.95、0.87,P<0.05)。结论PDR患眼纤维血管膜中HIF-2α表达高于对照组,且与DLL4、VEGF的表达均呈显著正相关。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

关 键 词：糖尿病视网膜病变 视网膜新生血管化 缺氧诱导因子1 

分 类 号：R774.1[医药卫生—眼科] R587.2[医药卫生—临床医学]