血管内皮生长抑制因子在糖尿病视网膜病变患者血清及玻璃体中的变化

背景糖尿病视网膜病变（DR）患者因视网膜缺血导致新生血管的形成，从而严重威胁患者视力。血管内皮生长抑制因子（VEGI／TLlA）作为一种血管生成抑制剂，具有强大的抗血管生成作用。目的检测VEGI／TLlA及其相关因子在DR患者血清及玻璃体中的变化。方法采用非随机对照研究方法，收集2012年11月至2013年3月在天津医科大学总医院眼科确诊为DR的患者55例，按照中国眼底病学组制定的DR分期标准分为非增生性糖尿病视网膜病变（NPDR）组20例，PDR组35例；另纳入无全身疾病的白内障患者11例作为正常对照组，取单纯糖尿病（DM）患者15例作为DM组，各组患者人口基线特征相匹配，但PDR组和DM组患者的病程值及血糖水平值明显高于DR组，差异均有统计学意义（均P〈0．05）。收集4个组所有受试者静脉血清以备ELISA检测。另收集2012年11月至2013年3月在天津医科大学总医院眼科确诊为PDR的患者23例25眼作为PDR组，健康成人尸体供眼7例7眼作为对照组，并根据PDR组患者的治疗方法分为视网膜光凝组、手术治疗组和视网膜光凝＋手术组，在手术过程中收集玻璃体待检。采用ELISA法检测血清及玻璃体中肿瘤坏死因子样配体1／血管内皮生长抑制因子251（TLlA／VEGI251）、血管内皮生长因子（VEGF）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和核因子-KBp65（NF—KBp65）的质量浓度。应用单因素方差分析和独立样本t检验比较并分析各组血清及玻璃体中TLlA／VEGI251、VEGF、TNF-α、IL-1β和NF—KBp65的差异，应用Pearson积矩线性相关分析法分析TLlA／VEGI251与VEGF、TNF-α、IL-1β和NF—KBp65的相关性。结果DM组、NPDR组、PDR组患者血清中TLlA／VEGI251质量浓度均明显高于正常对照组，4个组间总体差异有统计学意义（F=27．431，P=0．009）；PDR组患者血清中TLlA／VEGI251质量浓度明显高于DM组和NPDR组（P〈0．05）；PDR组患者血清中VEGF、TNF—α、IL-1β和NF—KBp65质量浓度均明显高于DM组、NPDR组和正常对照组，差异均有统计学意义（P〈0．05），而正常对照组、DM组和NPDR组之间比较差异均无统计学意义（P〉0．05）。患者血清中TLlA／VEGI251质量浓度与VEGF、TNF-α、IL-1β和NF—KBp65质量浓度间均呈明显正相关（r=0．951、0．951、0．851、0．944，均P〈0．01）。PDR组玻璃体中TLlA／VEGI251、VEGF、TNF-α、IL-1β质量浓度均明显高于正常对照组（P=0．024、0．001、0．000、0．037），但两组间玻璃体中NF—KBp65浓度比较差异无统计学意义（P=0．073）。视网膜光凝组及手术组患者玻璃体中TLlA／VEGI251质量浓度低于对照组（P〈0．05），玻璃体中TLlA／VEGI251质量浓度与VEGF和TNF-α质量浓度间均呈明显正相关（r=0．675、0．950，P〈0．01），与玻璃体中IL-1β和NF—KBp65质量浓度均无明显相关性（r=0．233、0．318，P〉0．05）。结论VEGI参与DR的发病，并通过与VEGF、TNF-α、IL-1β、NF—KB等因子的相互作用共同影响疾病的进展，为DR的进一步研究提供了新的思路。

Change of vascular endothelial growth inhibitor in serum and vitreous of diabetic retinopathy patients

Background Diabetic retinopathy （DR） leads to blindness because of the retinal angiogenesis caused by the ischemia of retina. Vascular endothelial growth inhibitor （VEGI） is a recently identified anti-angiogenic cytokine,which can suppress endothelial cell proliferation and angiogenesis. Objective The aim of this study was to detect the change of serum and vitreous VEGI/TL1A and its relative eytokines in patients with DR. Methods A non-randomized controlled clinical trial was performed. Fifty-five DR patients were enrolled in Tianjin Medical University General Hospital from November 2012 to March 2013 with the informed consent. The patients were divided into non-proliferative DR （NPDR） group （20 cases） and PDR group （35 cases）. Eleven cataract patients served asnormal control group,and 15 patients with diabetic mellitus （DM） were included as DM group. The demography was matched among the groups,but the course of DM and the blood glucose level were elevated in the PDR group and the DM group compared with DR group （ all at P〈0.05 ）. We collected the serum of all the patients above. Another 23 PDR patients （25 eyes） were enrolled in Tianjin Medical University General Hospital from November 2012 to March 2013 with the informed consent and served as PDR group,healthy corpse＇s eyes （n=7） as control group,the patients were assigned to the retinal photocoagulation group, surgery group and photocoagulation ＋surgery group according to different treatment procedures. Vitreous samples were collected during the progress of vitrectomy. TL1A/VEGI 251, VEGF, TNF-a, IL-113 and NF-KB p65 concentrations in the serum and vitreous specimens were detected using ELISA. The differences of serum and vitreous TL1A/VEGI 251, VEGF,TNF--α, IL-1β and NF-KB p65 in various groups were statistically analyzed by ANOVA and independent sample t test, respectively. The correlation between TL1A/VEGI 251 and VEGF,TNF--α,IL-1β, NF-KB p65 were calculated by Pearson correlation analysis. Results TL1A/VEGI 251 concentration was elevated in the DM group, NPDR group and PDR group compared with the normal control group, with significant difference among the 4 group （ F = 27.431, P = 0. 009 ） , and TL1A/VEGI 251 concentration was higher in the PDR group than that in the DM group or the NPDR group （P〈0. 05）. VEGF,TNF-α,IL-1β and NF-KB p65 concentrations in serum were increased in the PDR group in comparison with the DM group,NPDR group and the normal control group （P〈0.05）. However, no significant difference among the DM group, NPDR group and the normal control group （ P〉0.05 ）. Serum TL1A/VEGI 251 concentration was significant correlated with VEGF, TNF-α, IL-1β and NF-KB p65 concentration （r=0. 951,0. 951,0. 851,0. 944,all at P〈0. 01）. Vitreous TL1A/VEGI 251 ,VEGF, TNF-α, IL-1β concentrations were ascended in the PDR group compared with the normal control group （ P = 0. 024, 0. 001,0. 000,0. 037 ） ,but there was no significantly difference in vitreous NF-KB p65 concentration between the two groups （P = 0. 073）. Vitreous TL1A/VEGI 251 concentrations declined in the retinal photocoagulation group and the surgery group compared with the normal group （ all at P 〈 0.05 ） , and significant positive correlations were found between vitreous TL1A/VEGI 251 concentration and VEGF or TNF-αconcentration （ r= 0. 675,0. 950,P〈0.01 ） ; while Pearson correlation coefficient was not statistically significant between vitreous TL1A/VEGI 251 concentration and IL-1β or NF-KB p65 concentration （r=0.233,0.318,P〉0.05）. Conclusions VEGI is involved in the pathogenesis of DR, and it interacts with VEGF, TNF-α, IL-1β and NF-KB to affect the development of DR. These results provide a new clue for the further study of DR.