糖尿病视网膜病变患者血清VEGF、ES、TKLK、TSP、sICAM-1水平的变化及意义

目的:探讨血清血管内皮细胞生长因子(VEGF)、内皮抑素(ES)、血小板反应蛋白(TSP)、组织激肽释放酶(TKLK)及可溶性细胞间黏附分子-1(sICAM-1)水平在糖尿病视网膜病变(DR)患者血清中的变化及其临床意义.方法:选取我院2014-01/2016-12收集的无眼底病变的糖尿病患者60例(DM组)、非增殖性糖尿病视网膜病变患者60例(NPDR组)、增殖性糖尿病视网膜病变患者60例(PDR组)和同期健康体检对象60例(对照组),检测四组患者血清VEGF、ES、TSP、TKLK、sICAM-1水平并进行比较分析.结果:PDR组患者的血清VEGF、TKLK、sICAM-1水平均显著高于NPDR组、DM组、对照组(P<0.05);PDR组患者的血清ES水平均显著低于NPDR组、DM组、对照组(P<0.05).NPDR组患者的血清VEGF、TKLK、ES水平均显著高于DM组和对照组(P<0.05).NPDR组患者的血清VEGF与ES、TKLK、sICAM-1水平均呈显著的正相关关系(P<0.05).PDR组患者的血清VEGF与TKLK、sICAM-1水平均呈显著的正相关关系(P<0.05),PDR组患者的血清VEGF与ES、TSP相关性不显著(P>0.05).结论:DR患者血清ES、TSP、TKLK、sICAM-1水平均发生显著改变,通过调节VEGF水平影响DR进程.     

胰激肽释放酶治疗早期高血压视网膜病变

胰激肽释放酶（TPK）为微循环障碍改善剂，具有舒张血管的作用。临床主要用于治疗轻中度高血压、肢体动脉硬化闭塞症、脑动脉硬化、血栓形成及闭塞性周围血管病等。该药可能有改善视网膜微循环作用。作者对40例资料完整的高血压视网膜病患者，经用TPK治疗3mo，取得较好效果，现总结如下。1对象和方法1．1对象40例（80只眼）高血压视网膜病变患者均来自眼科门诊病例，其中男22例，女18例，年龄45～62a，平均54a，患高血压病平均为6a，排除肾脏及其它系统疾病。1．2方法用检眼镜、裂隙灯检查眼底，40例中有30例合并有眼底改变（Scheie）。…     

激肽系统与糖尿病视网膜病变

激肽系统广泛存在于动物体内,和体内多个系统及其他细胞因子有密切的联系和交叉对话,发挥重要作用。其广泛生物活性包括扩张血管、促进NO合成、促进血管新生以及增强血管渗漏等,在糖尿病视网膜病变中可能扮演一定角色。干预激肽系统用以治疗糖尿病视网膜病变可以有多种途径和方式,包括应用胰激肽酶原等,但确切疗效和副作用有待进一步观察。     

糖尿病视网膜病变患者血浆VEGF和CAMS水平的变化及其临床意义

目的探讨糖尿病视网膜病变患者血浆血管内皮细胞生长因子（vascular endothelial growth factor，VEGF）和细胞黏附分子（cellular adhesion molecules，CAMS）水平的变化及其临床意义。方法采用ELISA法检测58例糖尿病视网膜痛变（diabetic retinopathy，DR）患者血浆VEGF、可溶性细胞间黏附分子-1（soluble intercellular adhesion molecule，sICAM—1）和可溶性血管细胞间黏附分子-1（soluble vascular cellular adhesion molecule，sVCAM-1）的变化，并与非糖尿痛视网膜病变（non—diabetic retinopathy，NDR）患者进行比较。结果糖尿病患者血浆VEGF和sICAM—1、sVCAM—1明显高于对照组，差异有显著性（t’=28．581，20．765，t=19．667，P〈0．001）；DR患者血浆VEGF和sICAM—1、sVCAM—1明显高于NDR患者。差异有显著性（t=11．358～16．025，P〈0．001）；PDR患者VEGF和sICAM-1、sVCAM-1明显高于NPDR患者，差异有显著性（t=5．941～14．547，P〈0．001）。NPDR和PDR患者血浆VEGF与siCAM—1、sVCAM—1呈明显的正相关（r=0.617～0．720。P〈0．01）。结论血浆VEGF和sICAM-1、sVCAM—1水平变化参与了DR的发生与发展，且与病变程度有关。     

血管内皮细胞生长因子在糖尿病性视网膜病变进展中的作用

糖尿病性视网膜病变是糖尿病微血管病变常见而严重的并发症,在很大程度上导致不可逆的视功能损害或完全失明.VEGF在DR发生、发展,尤其在视网膜新生血管形成过程中发挥重要作用,本文就血管内皮生长因子与糖尿病性视网膜病变的关系进行综述。     

糖尿病视网膜病变患者血清C肽水平的变化

目的:观察血清C肽与糖尿病视网膜病变的关系。方法:2型糖尿病患者119例根据糖尿病视网膜病变程度分为3组,分别测定其空腹及餐后2h血清C肽的水平,并记录其他可能影响糖尿病视网膜病变发展的因素。结果:增生性糖尿病视网膜病变组空腹及餐后2h血清C肽均最低,背景型糖尿病视网膜病变组次之,logistic回归分析证明餐后2h血清C肽水平是影响糖尿病视网膜病变发展的独立因素。结论:餐后2h血清C肽水平降低是糖尿病视网膜病变发展的危险因素。     

血管内皮生长因子在糖尿病视网膜病变发病机制中的研究进展

血管内皮生长因子具有促进血管通透性增加、细胞外基质变性、血管内皮细胞迁移、增殖和血管形成等作用,在缺氧、胰岛素、糖基化终产物、血管紧张素Ⅱ(AngⅡ)、内毒素、生长因子等因素影响下,参与糖尿病视网膜病变的发生发展。本文就近年来国内外对VEGF的理化特性、生物学效应、各种影响因素作用的分子生物学机制以及VEGF参与糖尿病视网膜病变发生发展的研究进展作一综述。     

HIF-1调节机制在糖尿病视网膜血管及神经病变中的研究进展

糖尿病视网膜病变的实质是进展性的微血管病变,新生血管形成是其特征性的病理改变。在高糖和低氧环境下,低氧诱导因子-1α(HIF-1α)在血管新生和视神经纤维受损中起重要作用,它通过诱导VEGF和p53上调,从而促进眼内新生血管的发生和发展,同时也促使视网膜神经细胞抑制和凋亡。故本文对HIF-lα在糖尿病视网膜疾病中的研究进展作一综述。     

血管生成促进因子在糖尿病视网膜病变新生血管形成中的作用

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病最常见和最严重的并发症之一.目前,DR的发病机制尚不明确,但近年来研究表明,血管生成促进因子与DR新生血管的发生、发展密切相关,是导致视网膜新生血管形成的主要致病因子.本文就血管生成促进因子在DR新生血管形成中的作用进行综述.     

血清血小板内皮细胞黏附分子-1水平变化对糖尿病视网膜病变的影响

背景研究糖尿病视网膜病变（DR）发生发展的相关危险因素对DR的预防有重要意义,血小板内皮细胞黏附分子-1（PECAM-1）是介导糖尿病患者血管病变发生的重要介质,但其作用机制仍有待进一步研究。目的探讨2型糖尿病患者血清中PECAM-1水平变化对DR发生及发展的影响。方法收集在南通市第三人民医院内分泌科确诊的2型糖尿病患者共54例,根据检眼镜检查和荧光素眼底血管造影（FFA）结果,依据1987年中华医学会DR分期标准将患者分为无DR（NDR）组18例、非增生型糖尿病视网膜病变（NPDR）组20例和增生型糖尿病视网膜病变（PDR）组16例,并收集年龄和性别与患者相匹配的18名健康体检者作为正常对照组。收集患者外周血,用ELISA法检测患者血清中PECAM一1的质量浓度;用高效液相色谱法检测患者血清中糖化血红蛋白（HbAlC）含量;采用全自动生化分析仪检测患者的血糖水平;探讨DR患者PECAM—l质量浓度与HbAlC含量的关系,并将各组患者的检测结果进行比较。结果PDR组、NPDR组、NDR组和正常对照组患者血清中PECAM-1质量浓度分别为（10．907-4-2．792）、（7．024±2．377）、（5．231±1．816）和（3．817±1．045）μg／L,总体差异有统计学意义（F=12．630,P=0．002）,PDR组患者血清PECAM—l质量浓度明显高于NPDR组、NDR组和正常对照组,差异均有统计学意义（P〈0．05）。PDR组、NPDR组、NDR组和正常对照组患者血清HbAlC水平分别为（12．596±3．148）％、（9．118±3．356）％、（5．491±1．017）％和（4．992＋-0．725）％,总体比较差异有统计学意义（F=7．130,P=0．015）,PDR组、NPDR组患者血清HbAlc水平显著高于NDR组和正常对照组,PDR组PECAM一1和HbAlc水平明显高于NPDR组和正常对照组,差异均有统计学意义（P〈0．05）。PDR组、NPDR组、NDR组患者血清PECAM-1质量浓度与血清HbAlc水平间均呈显著正相关（r=0．799,P〈0．01;r=0．647,P〈0．01;r=0．685,P〈0．01）。病程≥10年的PDR组与NPDR组糖尿病病程比较差异有统计学意义（P=0．023）。结论PECAM一1高表达是促进DR发生和发展的重要因素,与患者的高血糖状态密切相关,预防DR应以治疗糖尿病、控制血糖为主。     

Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

AIM:To investigate the role of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in proliferative diabetic retinopathy (PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor (VEGF) expressions.METHODS: A total of 36 vitreous samples were collected from 36 patients with PDR (PDR group), and 17 vitreous samples from 17 patients with idiopathic macular hole were used as control. The concentrations of t-PA, PAI and VEGF in samples were determined by ELISA method. The correlations among t-PA, PAI and VEGF expressions were discussed.RESULTS: The concentrations of t-PA, PAI and VEGF in the PDR group were significantly higher than those in the control group (P<0.001). The t-PA and PAI expressions were highly correlated with the VEGF expression (P<0.001).CONCLUSION:In addition to VEGF, a variety of bioactive substances, such as t-PA and PAI, are involved in the pathogenesis involved in the angiogenesis of PDR. VEGF can activate t-PA expression, resulting in collagen tissue degradation and angiogenesis. VEGF may also activate the mechanism for endogenous anti-neovascularization.     

Elevation of serum apelin-13 associated with proliferative diabetic retinopathy in type 2 diabetic patients

AIM:To compare apelin-13, a ligand of G-protein-coupled receptor which has been shown to be involved in retinal angiogenesis, and vascular endothelial growth factor (VEGF) serum levels in type 2 diabetes mellitus (T2DM) with or without retinopathy, and to investigate the relationship between the serum concentration of apelin-13 and diabetes retinopathy.METHODS: Sixty-nine patients with T2DM were enrolled. Of the 69 patients, 16 had proliferative diabetic retinopathy (PDR group), 23 had non-PDR (NPDR group) and 30 had no retinopathy (T2DM group). Subjects’ information, including demographics, medical history, and use of medications were recorded. Their serum samples were collected for measuring the levels of C-reactive protein (CRP), serum lipid and glycosylated hemoglobin. Apelin-13 and VEGF serum levels were measured by enzyme-linked immunosorbent assay. Kruskal-Wallis test and one-way ANOVA were used to compare the differences among these groups. Chi-square test was used to assess categorical variables. Correlations between variables were investigated by Spearman rho correlation test and stepwise regression analysis. All statistical analyses were performed through SPSS 17.0 software.RESULTS:Sex, age, body mass index (BMI), blood pressure, CRP, hemoglobin A1c (HbA1c) have no significantly difference in the three groups. Serum level of apelin-13 was significantly elevated in PDR group as compared with T2DM group (P=0.041). Differences of VEGF serum concentration in the three groups were statistically significant (P=0.007, P=0.007 and P<0.001, respectively). Spearman rho correlation test showed that serum apelin-13 was positively correlated with BMI, serum triglycerides, VEGF, but not with age, duration of diabetes, blood pressure, CRP, HbA1c and total-cholesterol. Stepwise regression analysis showed that BMI also significantly associated with serum apelin-13 (P=0.002), while VEGF and serum triglycerides were irrelevant.CONCLUSION: This study elucidated a positive association of apelin-13 serum level with PDR, but not with VEGF. Apelin-13 may influence the promotion of PDR but unrelated with VEGF.     

Research progress on the role of connective tissue growth factor in fibrosis of diabetic retinopathy

Diabetic retinopathy (DR) is one of the most important types of diabetic microangiopathy, which is a specific change of fundus lesions and is one of the most serious complications of diabetes. When DR develops to proliferative DR, the main factors of decreasing vision, and even blindness, include retinal detachment and vitreous hemorrhage caused by contraction of blood vessels by fiber membrane. Recent studies reported that the formation of fiber vascular membrane is closely related to retinal fibrosis. The connective tissue growth factor (CTGF) is a cytokine that is closely related to DR fibrosis. However, its mechanism is poorly understood. This paper summarizes the recent studies about CTGF on DR fibrosis for a comprehensive understanding of the role and mechanism of CTGF in PDR.     

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age‐related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis‐dependent pathologies in the eye and non‐ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen‐induced retinopathy, laser‐induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF‐specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research.     

血管内皮生长因子及其受体与糖尿病视网膜病变

视网膜新生血管形成和黄斑水肿是糖尿病视网膜病变(diabeticretinopathy,DR)的主要临床表现,也是DR主要的致盲原因。目前研究表明血管内皮生长因子(vascularen-dothelialgrowthfactor,VEGF)在糖尿病视网膜微血管并发症的发生中发挥重要作用,因此VEGF成为当今DR治疗干预的一个研究热点。本文就VEGF及其受体在DR中的表达及其相关治疗措施进行综述。     

糖尿病视网膜病变细胞因子及视网膜血流变化的意义

目的:探讨VEGF、细胞因子及视网膜血流状态与糖尿病视网膜病变(DR)的相关性.方法:将174例糖尿病患者根据视网膜病变情况分为无DR组(NDR,41例)、背景DR(NPDR,68例)及增殖期DR组(PDR,65例)三组,纳入健康志愿者30例作为对照组.对所有受试者血清VEGF、肿瘤坏死因子-α(TNF-α)、可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)及碱性成纤维细胞生长因子(bFGF)水平进行测定,并对其进行眼部彩色多普勒超声检查,测量视网膜中央动脉的各项血流动力学参数.结果:糖尿病患者血清VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF水平显著高于对照组;PDR血清VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF水平显著高于NDR和NPDR组,NPDR组血清VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF水平又显著高于NDR(P＜0.05).糖尿病患者Vmax,Vmin,Vmean和PI显著低于对照组,RI显著高于对照组;PDR组Vmax,Vmin,Vmean和PI显著低于NDR和NPDR组,RI显著高于NDR和NPDR组;NPDR组Vmax,Vmin,Vmean和PI又显著低于NDR,RI则显著低于NDR和NPDR组(P＜0.05).结论:VEGF,TNF-α,sICAM-1,sVCAM-1,bFGF以及CRA血流动力学改变与DR的发生发展密切相关,在DR诊断和治疗中具有参考意义.     

糖尿病性视网膜病变患者房水中VEGF与IGF-1的定量测定及分析

目的:探讨糖尿病视网膜病变(DR)程度与房水中VEGF、IGF-1含量之间的关系。方法:研究对象共44例,分为正常对照组(A组)、糖尿病患者无视网膜病变组(NDR组)(B组)、糖尿病性视网膜病变组(DR组)(C组),其中C组又分为单纯型糖尿病性视网膜病变组(BDR组)(C1组)和增殖型糖尿病性视网膜病变组(PDR组)(C2组)。对所有研究对象均收集房水标本。对标本均采用双抗体夹心ABC-ELISA法进行人VEGF和人IGF-1定量ELISA测定。结果:随着糖尿病的进展及DR的逐渐加重,房水中VEGF浓度呈明显增加趋势。房水IGF-1:对照组(A组)、NDR组(B组)、DR组(C组)各组间P<0.01,呈明显增高趋势。BDR组(C1组)与PDR组(C2组)间P<0.01,呈明显增高趋势。房水VEGF与房水IGF-1二者有显著正相关性(P<0.01)。结论:VEGF是影响糖尿病眼底微血管病变发生、发展的重要刺激因子;眼内IGF-1参与了DR进展的病理进程;在DR的发生发展过程中,IGF-1与VEGF有协同作用。     

VEGF在糖尿病视网膜病变发病机制中作用的研究新进展

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病最常见的微血管并发症之一,其基本病理改变是血-视网膜屏障(blood-retinal barrier,BRB)破坏、新生血管形成,后期新生血管膜收缩牵拉引起视网膜脱离。DR的发病机制十分复杂,至今尚未完全阐明。任何病理改变在本质上均是体内动态平衡的失调,新生血管的形成亦然,血管刺激因素增强和(或)抑制因素减少使两者平衡失调即所谓的"血管生成开关"形成。血管内皮生长因子(vascularendothelial growth factor,VEGF)是体内促新生血管形成的主要因子之一,近年来在DR的发病机制以及治疗的研究中广受关注。我们旨在阐述VEGF在DR发病机制中的作用。