血清中血管内皮生长因子、白细胞介素-2及肿瘤坏死因子α在糖尿病视网膜病变中的作用

Role of vascular endothelial growth factor, interleukin-2 and tumor necrosis factor-alpha in diabetic retinopathy

背景糖尿病视网膜病变（DR）是一种严重的糖尿病并发症，其确切的发病机制尚不清楚，有研究认为细胞因子增加单核细胞和内皮细胞黏附的过程，进而引起视网膜毛细血管炎症反应是DR发生发展的关键因素。目的检测2型DR患者血清中血管内皮生长因子（VEGF）、白细胞介素-2（IL-2）、肿瘤坏死因子α（TNF—α）的质量浓度，并探讨其临床意义。方法采用前瞻性病例对照研究设计。对90例2型糖尿病患者血清中VEGF、IL-2和TNF-α的质量浓度采用双抗体夹心ELISA法进行检测。根据散瞳后眼底检查和荧光素眼底血管造影（FFA）检查，将实验组分为无DR组30例、单纯性DR组30例、增生型糖尿病视网膜病变（PDR）组30例，对照组为健康体检者30名。结果无DR组、单纯性DR组、PDR组血清中VEGF的质量浓度为（217．35±27．87）、（298．31±49．26）、（341．23±40．18）ng／L，IL-2的质量浓度为（12．12±1．57）、（16．43±2．26）、（21．36±0．86）ng／L，TNF-α的质量浓度为（11．63±0．94）、（17．52±0．65）、（22．01±0．87）ng／L，与对照组VEGF、IL-2和TNF—α的质量浓度（193．46±37．39）、（8．99±0．57）、（7．31±0．52）ng／L比较，4个组间差异均有统计学意义（F=126．380，P〈0．01；F=120．370，P〈0．01；F=99．840，P〈0．01）。对照组、无DR组、单纯性DR组与PDR组血清VEGF、IL-2、TNF—α的质量浓度有依次增加的趋势。各组患者血清中的VEGF、IL-2、TNF—α质量浓度间存在正相关关系（r=0．749，P〈0．01；r=0．631，P〈0．01）。无DR组、单纯性DR组、PDR组间病程比较差异有统计学意义，且有明显增加的趋势（F=137．230，P〈0．01）；各DR组血清中VEGF、IL-2、TNF-α质量浓度组与病程均呈正相关（r=0．791，P〈0．01；r=0．665，P〈0．01；r=0．632，P〈0．01）。结论VEGF、IL-2及TNF-α存DR的发病和进展过程中起重要作用。

Background Diabetic retinopathy （DR） is a progressive vision-threatening complication of diabetes mellitus,but its pathogenic mechanism is still unclear. Recent studies showed that it may be associated with the inflammation response of retinal capillary. Cytokines can cause induction of proinflammatory and adhesion molecules and thereby increase monocyte endothelial cell adhesion,which is now accepted as the early key event in the development of DR. Objective The present study was to determine the relationship between the stages of DR and the levels of serum vascular endothelial growth factor（VEGF） , interleukin-2 （IL-2） , tumor necrosis factor-alpha （TNF-α） in diabetic patients. Methods This was a pilot case-controlled study. Ninety patients with type 2 diabetes mellitus were included in this clinical trial and 30 healthy individuals were enrolled as controls. The patients were grouped into the non-diabetic retinopathy （NDR） group, background DR group and proliferative DR （PDR） group according to the results from ophthalmoscopic examination and fundus fluorescein angiography （FFA） , with 30 patients for each group. The levels of serum VEGF,IL-2,TNF-α were assayed by ELISA and compared among the 4 groups. Written informed consent was obtained from each subject before received any related medical examination to this study. Results The mean serum VEGF levels were（217.35±27.87）ng/L,（298.31±49.26）ng/L,and（341.23± 40. 18 ） ng/L, respectively, and mean serum IL-2 levels were （ 12.12 ±1.57 ） ng/L, （ 16.43 ± 2.26 ） ng/L, and （ 21.36± 0.86 ） ng/L, respectively and mean serum TNF-α levels were （ 11.63±0.94 ） ng/L, （ 17.52±0.65 ） ng/L, and （ 22.01 ± 0. 87 ）ng/L respectively in the patients with NDR,background DR and PDR, showing significant differences from healthy controls with（ 193.46±37.39 ） ng/L for serum VEGF, （ 8.99 ±0. 57 ） ng/L for serum IL-2 and （ 7.31 ±0. 52 ） ng/L for serum TNF-α（ F = 126. 38, P〈0. 01 ;F= 120. 37, P〈0. 01 ;F= 99.84, P〈0. 01 ）. The levels of serum VEGF, IL-2, and TNF-α in the patients with the NDR,background DR and PDR were increased significantly. The level of serum VEGF showed the positively significant correlation with serum IL-2 level and TNF-α level （ r = 0. 749, P 〈 0.01 ; r = 0.631, P〈0.01 ）. The serum levels of VEGF, IL-2 and TNF-α showed a significantly positive correlation with the prolongation and severity ofDR（r=0. 791,P〈0.01;r=0. 665,P〈0.01;r=0. 632,P〈0. 01）. Conclusions VEGF,IL-2 and TNF-α play active roles in the generation and development of diabetic retinopathy, and the level of serum VEGF is closely associated with the levels of serum IL-2 and TNF-α. during the development of DR.