新生血管性青光眼患者房水和血浆中VEGF、TGF-β1和IL-6的测定及意义

摘要

背景 新生血管性青光眼(NVG)以虹膜和房角新生血管为主要特征,发病机制尚未完全阐明.研究证实多个细胞因子和炎性因子与新生血管的形成有关,但这些细胞因子与NVG的关系研究尚不完全清楚. 目的 探讨NVG患者房水和血浆中血管内皮生长因子(VEGF)、转化生长因子β1(TGF-p1)和白细胞介素-6(IL-6)质量浓度的变化及其意义.方法 采用前瞻性病例对照研究方法,纳入2014年5月至2015年3月于上海市东方医院确诊的NVG患者8例8眼、原发性开角型青光眼(POAG)患者10例10眼及年龄相关性白内障(ARC)患者10例10眼.眼部手术前1d收集患者空腹肘静脉血3～4 ml,离心后取上清液0.3～0.4 ml,于眼部手术时收集房水0.1 ～0.2 ml,采用ELISA法分别检测患者房水及血浆中VEGF、TGF-β1和IL-6质量浓度,对检测结果进行组间比较. 结果 NVG组患者房水和血浆中VEGF质量浓度分别为(2 769.85±390.88) pg/ml和(529.93±95.20) pg/ml,明显高于POAG组的(208.12±58.59) pg/ml和(219.28 ±24.44) pg/ml及ARC组的(158.88±12.35) pg/ml和(172.82±31.91) pg/ml,组间总体比较差异均有统计学意义(房水:F=433.80,P＜0.01;血浆:F=103.84,P＜0.01).NVG组患者房水和血浆中TGF-β1质量浓度分别为(157.94±113.00) pg/ml和(3 895.78±2 318.00) pg/ml,明显高于POAG组的(54.48±35.58) pg/ml和(2 196.13±1 185.39)pg/ml以及ARC组的(47.98±17.69) pg/ml和(1 937.28±933.27) pg/ml,组间总体比较差异有统计学意义(房水:F=7.88,P＜0.01;血浆:F=4.18,P＜0.05).NVG组房水和血浆中IL-6质量浓度分别为(234.87±41.64) pg/ml和(26.97±8.19) pg/ml,明显高于POAG组的(38.97±19.06) pg/ml和(19.54±5.11) pg/ml以及ARC组的(29.48±14.61) pg/ml和(18.50±3.57) pg/ml,组间总体比较差异均有统计学意义(房水:F=166.27,P＜0.01;血浆:F=5.59,P＜0.05). 结论 NVG患者房水及血浆中VEGF、TGF-β1、IL-6质量浓度明显高于POAG及ARC患者,提示3种细胞因子均参与NVG的发生及虹膜新生血管的形成,可能成为NVG治疗的靶点.%Background Neovascular glaucoma (NVG) is a refractory disease characterized by neovascularization,and its pathogenesis mechanism is still unelucidated.Researches showed that muhicytokins and inflammatory factors are associated with neovascularization,however,the correlation of these factors with NVG worth attention.Objective This study was to detect the vescular endothelial growth factor (VEGF),transforming growth factor β1 (TGF-β1) and interleukin-6 (IL-6) levels in aqueous humor and plasma in NVG eyes and its significance.Methods A prospective cases-controlled study was performed under the approval of Ethic Committee of Shanghai East Hospital and informed consent of patients.Eight eyes of 8 NVG patients,10 eyes of 10 primary open angle glaucoma (POAG) patients and 10 eyes of age-related cataract (ARC) patients were entrolled in Shanghai East Hospital from May,2014 to March,2015.The periphery blood of 3-4 ml was collected from all the patients to prepare 0.3-0.4 ml serum,and 0.1-0.2 ml aqueous humor was collected during the surgery from each eye.The aqueous and serum levels of VEGF,TGF-β1 and IL-6 were measured by ELISA.Results The aqueous humor and plasma VEGF concentrations in NVG patients were (2 769.85 ± 390.88) pg/ml and (529.93 ± 95.20) pg/ml,respectively,which were higher than (208.12 ± 58.59) pg/ml and (219.28 ± 24.44) pg/ml in POAG patients as well as (158.88 ±12.35) pg/ml and (172.82±31.91)pg/ml in ARC patients,with significant differences among the three groups (aqueous:F=433.80,P＜0.01;plasma:F=103.84,P＜0.01).The levels of TGF-β1 in aqueous humor and plasma from NVG patients were (157.94±113.00)pg/ml and (3 895.78±2 318.00)pg/ml,showing significant increases in comparison with (54.48±35.58) pg/ml and (2 196.13±1 185.39) pg/ml in the POAG patients or (47.98±17.69) pg/ml and (1937.28±933.27) pg/ml in the ARC patients (aqueous:F =7.88,P＜0.01;plasma:F =4.18,P＜0.05).The concentration of IL-6 in aqueous humor and plasma were (234.87±41.64) pg/ml and (26.97±8.19) pg/ml from NVG patients,with considerable elavation in comparison with (38.97± 19.06)pg/ml and (19.54±5.11)pg/ml in the POAG patients or (29.48±14.61) pg/ml and (18.50±3.57) pg/ml in the ARC patients (aqueous:F =166.27,P＜0.01;plasma:F=5.59,P＜0.05).Conclusions The aqueous and plasma VEGF,TGF-β1 and IL-6 are considerably higher in NVG patients than those in POAG patients and ARC patients,suggesting that these cytokines participate in the pathogenesis and development of the NVG and probably are treating target of NVG.