康柏西普对增生性糖尿病视网膜病变患者氧化应激水平和炎症因子浓度的影响

The effection of anti-VEGF(Conbercept)on oxidative stress level and inflammatory factor concentration of aqueous humous in patients of proliferative diabetic retinopathy

目的通过测定增生性糖尿病视网膜病变(PDR)患者玻璃体腔注射抗血管内皮生长因子(VEGF)药物前后,眼房水中白介素-6(IL-6)、人单核细胞趋化蛋白-1(MCP-1)和丙二醛(MDA)水平的变化及之间的相关性,探讨康柏西普对PDR患者房水中氧化应激水平和炎症因子浓度的影响。方法前瞻性临床研究。选取行玻璃体腔注射康柏西普,并行玻璃体切除术的PDR的患者共74例(75只眼)入组,其中男性35例,女性39例。每位患者在玻璃体注射康柏西普之前,前房穿刺取未经稀释的房水50~100μl;1周后在行玻璃体切除术之前,前房穿刺取未经稀释的房水50~100μl。排除有其他严重的心脏、肝、肾等全身疾病史者;有青光眼,葡萄膜炎等其他眼部疾病病史者;以前有过视网膜激光、玻璃体注射药物史,眼部手术史者。所有患者均检测玻璃体腔注射抗VEGF药前后眼房水中的IL-6、MCP-1、MDA浓度。结果玻璃体注射康柏西普7 d,房水中IL-6、MCP-1中位数水平(803.12 pg/ml、1213.28 pg/ml)较注射前(32.32 pg/ml,986.91 pg/ml)显著升高,差异有统计学意义(P<0.01);MDA中位数水平(20.63 pg/ml)较注射前(28.71 pg/ml)显著降低,差异有统计学意义(P<0.01)。Spearman’s相关分析显示,患者房水中IL-6和MCP-1浓度在注射康柏西普前后始终存在比较强的相关性,其中注射前r=0.681,P<0.001,注射后r=0.614,P<0.001。IL-6和MCP-1本身在注射前后也存在较强的相关性,其中IL-6注射前后r=0.376,P<0.05,MCP-1注射前后r=0.638,P<0.001。在注射康柏西普前,患者房水中MDA和MCP-1存在较强的相关性,r=0.651,P<0.001。MDA和IL-6也存在较强的相关性,r=0.530,P<0.05。在注射康柏西普后,没有发现MDA和MCP-1、IL-6的相关性。结论炎症反应与氧化应激之间的相互作用是PDR的发生发展中的一个比较重要的机制。

Objective The purpose of this study was to determine the levels of interleukin-6(IL-6),human monocyte chemoattractant protein-1(MCP-1)and malondialdehyde(MDA)in aqueous humor before and after intravitreal injection of anti-vascular endothelial growth factor(VEGF,Conbercept)in patients with proliferative diabetic retinopathy(PDR)and to discuss the correlation of these cytokines and MDA to further explore the effect of anti-vegf drug on oxidative stress level and inflammatory factor concentration in aqueous humor of patients with PDR.Methods Prospective clinical study.A total of 74 patients with proliferative diabetic retinopathy underwent pars plana vitrectomy(PPV)were enrolled in this study,including 35 males and 39 females.All the patients received intravitreal Conbercept theraphy 7 days before PPV.50~100μl of undiluted aqueous humor samples were collected at the time of intravitreal Conbercept and PPV treatment.Exclude patients with other serious history of heart,liver,kidney and other systemic diseases;glaucoma,uveitis and other history of eye diseases;previously had a history of retinal laser,vitreous injection,history of eye surgery.All patients were tested for IL-6,MCP-1,and MDA concentrations in the aqueous humor before and after intravitreal injection of anti-VEGF drugs.Results 7 days after intravitreal Conbercept,the levels of IL-6,MCP-1(803.12 pg/ml、1213.28 pg/ml)in aqueous humor were significantly higher than the levels of pre-operation(32.32±pg/ml,986.91 pg/ml),the difference was statistically significant(P<0.01).The levels of MDA(20.63 pg/ml)in aqueous humor were significantly lower than the levels of pre-operation(28.71 pg/ml),the difference was statistically significant(P<0.01).Spearman's correlation analysis showed that there were always strongly correlations between the concentrations of IL-6 and MCP-1 in the aqueous humor of the patients before and after the intravitreal Conbercept,including r=0.681 before injection,P<0.001,and r=0.614 after intravitreal injection,P<0.001.Il-6 and MCP-1 were also strongly correlated before and after intravitreal injection themselves,with IL-6 r=0.376,P<0.05,and MCP-1 r=0.638,P<0.001.We also find before the intravitreal Conbercept,there was a strong correlation between MDA and MCP-1 in the aqueous humor of patients,r=0.651,P<0.001.There was also a strong correlation between MDA and IL-6,r=0.530,P<0.05.No correlation between MDA,MCP-1,and IL-6 was found after intravitreal Conbercept.Conclusions The interaction between inflammatory mediators and oxidative stress may be an important mechanism in the development of proliferative diabetic retinopathy.