血管生成素-2及超敏C-反应蛋白与2型糖尿病视网膜病变的关系

Association of angiopoietin-2 and hypersensitive C-reaction protein with diabetic retinopathy in patients with type 2 diabetes mellitus

目的探讨2型糖尿病(T2DM)患者血清中血管生成素-2(Ang-2)、血管内皮细胞生长因子(VEGF)及超敏C-反应蛋白(hs-CRP)水平与视网膜病变(DR)进展的关系,为预防与治疗DR提供新的思路和方法。方法选取2010年6月至2012年3月在绍兴市人民医院内分泌代谢科住院的151例T2DM患者为研究对象,并依据1985年全国眼底病学术会议制定的DR分期标准和眼底荧光血管造影的情况将151例T2DM患者分为糖尿病无视网膜病变组(NDR)50例、非增殖性糖尿病视网膜病变组(NPDR)57例、增殖性糖尿病视网膜病变组(PDR)44例。同时检测患者血清中hs-CRP、Ang-2及VEGF水平。结果 3组患者血清中Ang-2、hs-CRP、VEGF水平比较,差异均有统计学意义(P<0.05),NPDR组Ang-2、hs-CRP、VEGF水平[分别为4.22(2.50,5.48)ng/ml、3.26(1.62,5.10)mg/L、300.00(78.70,495.60)pg/ml]明显高于NDR组[2.67(1.41,4.25)ng/ml、1.58(1.00,2.72)mg/L、159.80(40.83,376.42)pg/ml],而PDR组Ang-2、hs-CRP、VEGF水平[(6.30(3.92,8.20)ng/ml、5.00(3.15,8.74)mg/L、487.50(299.15,800.75)pg/ml]均明显高于NPDR组、NDR组。Spearman相关分析表明,DR患者血清中Ang-2与VEGF、hs-CRP呈正相关(r值分别为0.414、0.761,P<0.05),与糖尿病病程、体质指数(BMI)、糖化血红蛋白(Hb A1C)无明显相关性。多因素logistic回归分析显示,Ang-2(OR=1.241,P<0.05)、hs-CRP(OR=1.615,P<0.05)、VEGF(OR=1.002,P<0.05)、糖尿病病程(OR=1.113,P<0.05)是DR的独立危险因素。结论血清中Ang-2及hs-CRP水平与DR的严重程度相关,Ang-2可能通过介导血管内皮细胞功能异常及慢性炎症反应参与DR的发生和发展。

Objective To explore the association of angiopoietin-2（Ang-2）, vascular endothelial growth factor（VEGF）, hypersensitive C-reaction protein（hs-CRP） with the progression of diabetic retinopathy（DR） in patients with type 2 diabetes mellitus（T2DM）, and to provide the base for preventing and treating T2 DM. Methods One hundred fifty one T2 DM patients selected from inpatients of our department during June of 2010 to March of 2012 were served as the subjects. The subjects were divided into 3groups： no diabetic retinopathy group（NDR, 50 cases）, non-proliferative retinopathy group（NPDR, 57 cases） and proliferative diabetic retinopathy group（PDR, 44 cases）. The serum levels of Ang-2, VEGF and hs-CRP were detected for all subjects.Results The serum levels of Ang-2, hs-CRP and VEGF in NPDR group were 4.22（2.50, 5.48）ng/ml, 3.26（1.62, 5.10） mg/L and 300.00（78.70, 495.60） pg/ml. The serum levels of Ang-2, hs-CRP and VEGF in NDR group were 2.67（1.41, 4.25） ng/ml,1.58（1.00, 2.72） mg/L and 159.80（40.83, 376.42） pg/ml. There was a significant difference between NPDR group and NDR group（P〈0.05）. The serum levels of Ang-2, hs-CRP and VEGF in PDR group were 6.30（3.92, 8.20） ng/ml, 5.00（3.15, 8.74） mg/L and 487.50（299.15, 800.75） pg/ml. There was a significant difference between PDR group and NPDR group（P〈0.05）. Spearman correlation analysis showed Ang-2 was positively correlated with VEGF and hs-CRP（r values were 0.414 and 0.761, P〈0.05）,but no correlation between Ang-2 and duration of diabetes, BMI or Hb A1 Cwas found in DR group. Multivariate logistic regression analysis indicated that Ang-2（OR=1.241, P〈0.05）, hs-CRP（OR=1.615, P〈0.05）, VEGF（OR=1.002, P〈0.05） and diabetes duration（OR=1.113, P〈0.05） were independent risk factors of diabetic retinopathy. Conclusion Levels of serum Ang-2 and hs-CRP are associated with the severity of DR. Ang-2 might be involved in the occurrence and development of DR by inducing vascular endothelial cell dysfunction and chronic inflammation.