早期糖尿病视网膜病变患者外周血CXC趋化因子水平变化的临床意义

Clinical significance of detecting CXC chemotatic factor in early diabetic retinopathy

背景糖尿病视网膜病变（DR）是机体细胞因子网络紊乱的结果，新生血管启动因子（EI．R^＋CXC族趋化因子）和血管生成抑制因子（ELR-CXC族趋化因子）的失衡则是血管新生的启动因素。目的悬浮抗体芯片法同步检测2型糖尿病人群患者中外周血CXC趋化因子水平，采用受试者工作特征（ROC）曲线比较、筛选不同DR阶段CXC趋化因子的表达水平，筛选出可用于监测早期DR病情的因子，探讨CXC趋化因子在DR临床监测中的作用。方法前瞻性调查研究。以荧光素眼底血管造影结果作为分组金标准，66例出现DR的2型糖尿病患者为DR组，并将其分为轻度非增生型糖尿病视网膜病变（NPDR）组和中重度NPDR组，检测患者外周血中CXC趋化因子和血管增生因子的表达情况。以30例尚未出现DR的2型糖尿病患者为无DR组，应用ROC曲线下面积（AUC）进行比较筛选。结果年龄、病程2个指标在DR不同阶段差异均有统计学意义（F=8．507，P=0．001；F=28．143，P=0，000）。与无DR组比较，轻度NPDR组差异有统计学意义的指标还有生长相关癌基因-d（GROα）（t=-2．172，P=0．035，AUC=0．625）、全血黏度200（t=-3．724，P=0．001，AUC=0．904）和中性粒细胞（t=-2．562，P=0．0l3，AUC=0．577），中重度NPDR组差异有统计学意义的指标还有干扰素1诱导蛋白10（IP-10）（t=-3．591，P=0．001，AUC=0．592）、血小板衍生生长因子．BB（PDGF-BB）（t=-3．233，p=0．003，AUC=0．735）、血管内皮生长因子（VEGF）（t=-3．617，P=0．001，AUC=0．776）、C肽（t=-3．366，P=0．002，AUC：0．962）、白细胞（t=-3．201，P=0．003，AUC=0．852）和中性粒细胞（t=-4．201，P=0．000，AUC=0．852）。结论ELR’CXC和ELR-CXC趋化因子的失衡在DR早期发生发展过程中可能存在促发作用，GROct和IP-10对于临床监测DR病情的严重程度有-定价值，CXC趋化因子失衡状态的评估可以成为DR临床监测和预后评估的新途径。

Background Diabetic retinopathy （DR） is the result of the cytokine network disorders, the imbalance of angiogenie factor and vascular inhibitory factor is the start factor. Objective To analyze the levels of CXC ehemotatie factors of type 2 diabetes mellitus patients,evaluate the clinical application value of them in different clinical types of DR using receiver operating characteristic （ ROC ） analysis and to approach the new way of individualized treatment. Methods This was a prospective research. The gold standard was ophthalmolscope and fundus fluorescein angiography. The levels of CXC chemotatic factors and muhiplicaiton factors were measured in 96 cases with type 2 diabetes mellitus （66 cases with retinopathy and 30 cases without retinopathy as control）. The assessment tasks were performed for these index and courses of DR with ROC curve. Results The expression of age, course of disease has significant difference in different courses of DR （ F = 8. 507, P = 0.001 ; F = 28. 143, P = 0. 000）. Compared with the control group, the expression of growthrelated oncogene-c~ （GROc~） （ t = -2. 172, P = 0. 035, AUC = 0. 625 ） , whole blood viscosity 200 （ t = - 3. 724, P = 0. 001 , AUC = 0. 904 ） and neutrophilic leukocyte （t=-2. 562, P= 0. 013, AUC = 0. 577 ） has significant difference in the group of mild NPDR. Compared with the control group,the expression of interferonγinducible protein 10 （ IP-10 ） （ t = -3. 591, P = 0. 001 , AUC = 0. 592 ） ,platelet derivation growth factor-BB （PDGF-BB） （ t = -3. 233, P = 0. 003, AUC = 0. 735 ） , vascular endothelial growth factor（VEGF） （ t = -3. 617, P = 0. 001, AUC = 0. 776 ）, C peptide （ t = - 3. 366, P = 0. 002, AUC 0. 962 ）, leukocyte （t=-3.201,P= 0.003,AUC = 0.852） and neutrophilic leukocyte（t = -4.201,P = 0.000, AUC = 0.852） has significant difference in the group of moderate and severe NPDR. Conclusions CXC chemotatic factors may act as reaetivator in the pathogenesis of DR, GROct and IP-10 may be useful for clinical monitoring of thv severity of DR,and evaluating the imbalance state of chemotatic factors maybe a new approach to clinical monitoring and prognosis of DR.