增生型糖尿病视网膜病变患眼玻璃体腔注射康柏西普治疗前后房水细胞因子变化及其相关性分析

Changes and correlation analysis of cytokines in aqueous humor before and after intravitreal injection of conbercept treatment in patients with proliferative diabetic retinopathy

目的观察并分析增生型糖尿病视网膜病变(PDR)患眼玻璃体腔注射康柏西普(IVC)治疗前后房水细胞因子变化及其相关性。方法前瞻性临床研究。2019年3~12月于广州中医药大学第一附属医院眼科行IVC联合玻璃体切割手术(PPV)治疗的PDR患者36例42只眼(观察组)以及同期白内障手术患者27例31只眼(对照组)纳入研究。观察组患眼PPV前5~7 d行IVC治疗,IVC治疗中和二期PPV中分别抽取房水;对照组患眼于白内障手术中抽取房水。采用Luminex法检测两组患眼房水中VEGF-A、胎盘生长因子(PLGF)、血小板源性生长因子(PDGF)-AA、PDGF-BB、血管生成素样蛋白4(ANGPTL4)、IL-6、IL-8、IL-1β、单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)、TNF-α细胞因子表达。正态分布数据,两独立样本比较采用独立样本t检验;对非正态分布数据,两独立样本比较采用Wilcoxon秩和检验。相关性分析采用Spearman秩相关检验。结果IVC治疗前,观察组患眼房水中细胞因子VEGF-A、PLGF、PDGF-AA、ANGPTL4、IL-6、IL-8、MCP-1、ICAM-1浓度高于对照组,差异均有统计学意义(P<0.05)。与IVC治疗前比较,IVC治疗后观察组患眼房水细胞因子VEGF-A浓度降低,ANGPTL4、IL-8浓度升高,差异均有统计学意义(P<0.05);IVC治疗前后房水细胞因子PLGF、PDGF-AA、PDGF-BB、IL-6、IL-1β、MCP-1、ICAM-1、TNF-α浓度差异无统计学意义(P>0.05)。IVC治疗前房水细胞因子VEGF-A与PLGF、PDGF-AA、PDGF-BB、ANGPTL4、IL-6、IL-8、MCP-1、TNF-α均呈正相关(P<0.05)。结论PDR患者PPV前IVC治疗可降低房水中VEGF-A浓度,提高ANGPTL4、IL-8浓度。

Objective To study the changes and correlation of cytokines in aqueous humor before and after intravitreal injection of conbercept(IVC)treatment in patients with proliferative diabetic retinopathy(PDR).Methods A prospective clinical study.From March to December 2019,36 patients(42 eyes)of PDR patients treated with IVC combined with pars plana vitrectomy(PPV)(the observation group)and 27 patients(31 eyes)underwent cataract surgery in the same period(control group)in Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine were included in this study.Before PPV 5-7 days,IVC treatment was performed,and the aqueous humor were extracted during IVC and second-stage PPV in the observation group.The aqueous humor was extracted during cataract surgery in the control group.Luminex assay was used to detect VEGF-A,placental growth factor(PLGF),platelet-derived growth factor-AA(PDGF-AA),platelet-derived growth factor-BB(PDGF-BB),angiopoietin-like protein 4(ANGPTL4),IL-6,IL-8,IL-1β,monocyte chemoattractant protein-1(MCP-1),intercellular adhesion molecule-1(ICAM-1),tumor necrosis factor-α(TNF-α)cytokine expression.For normally distributed data,the independent sample t test was used for comparison between two independent samples;for non-normally distributed data,the Wilcoxon rank sum test was used for comparison between two independent samples.The correlation analysis used Spearman rank correlation test.Results Before IVC treatment,the concentrations of VEGF-A,PLGF,PDGF-AA,ANGPTL4,IL-6,IL-8,MCP-1 and ICAM-1 in the aqueous humor of PDR patients were significantly higher than those in the control group(P<0.05).After IVC treatment,the concentration of VEGF-A in the aqueous humor was significantly lower than that before treatment,and the concentrations of ANGPTL4 and IL-8 were significantly higher than those before treatment(P<0.05).There were no significant differences in the concentrations of PLGF,PDGF-AA,PDGF-BB,IL-6,IL-1β,MCP-1,ICAM-1 and TNF-αbefore and after IVC treatment(P>0.05).Before IVC treatment,the concentration of VEGF-A was positively correlated with PLGF,PDGF-AA,PDGF-BB,ANGPTL4,IL-6,IL-8,MCP-1 and TNF-α(P<0.05).Conclusions IVC treatment can reduce the concentration of VEGF-A and increase the concentrations of ANGPTL4 and IL-8 in aqueous humor in PDR patients before PPV.