福辛普利、转化生长因子β1与糖尿病视网膜病变

目的探讨血清转化生长因子β1(TGFβ1)在糖尿病视网膜病变(DR)发病中的意义以及血管紧张素转化酶抑制剂(ACEI)福辛普利对DR患者的治疗效果及对DR患者血清TGFβ1水平的影响。方法将80例2型糖尿病(2-DM)患者及20例健康人群分为5组,采用双抗体夹心酶联免疫吸附法(ELISA)检测其血清TGFβ1水平并进行比较。将45例背景型DR患者分为2组,25例福辛普利治疗组给予福辛普利治疗6个月,行眼底荧光造影(FFA)检查观察患者治疗前后眼底病变的变化并与药物对照组比较,同时检测患者治疗前后血清TGFβ1水平的改变。结果糖尿病组与正常对照组比较,血清TGFβ1水平升高,差异有显著性意义(P<0.01)。糖尿病三组之间比较,PDR组血清TGFβ1水平高于背景型DR组;背景型DR组血清TGFβ1水平高于NoDR组,三组之间差异均有显著性意义(P<0.05)。福辛普利治疗后背景型DR患者血清TGFβ1水平及UAER降低,与治疗前比较,差异均有显著性意义(P<0.05)。福辛普利治疗组治疗前后DR眼底的变化与药物对照组比较,无显著性差异(P>0.05)。结论DR患者血清TGFβ1水平显著升高,且随病变进展进一步升高,TGFβ1可能在DR发病及其进展中发挥重要作用。福辛普利通过抑制背景型DR患者产生TGFβ1,从而发挥可能对视网膜的保护作用,但短期内观察眼底的病变无明显改善。     

福辛普利、转化生长因子β_1与糖尿病视网膜病变

目的探讨血清转化生长因子β1(TGFβ1)在糖尿病视网膜病变(DR)发病中的意义以及血管紧张素转化酶抑制剂(ACET)福辛普利对DR患者的治疗效果及对DR患者血清TGFβ1水平的影响。方法将80例2型糖尿病(2-DM)患者及20例健康人群分为5组,采用双抗体夹心酶联免疫吸附法(ELISA)检测其血清TGFβ1水平并进行比较。将45例背景型DR患者分为2组,25例福辛普利治疗组给予福辛普利治疗6个月,行眼底荧光造影(FFA)检查观察患者治疗前后眼底病变的变化并与药物对照组比较,同时检测患者治疗前后血清TGFβ1水平的改变。结果糖尿病组与正常对照组比较,血清TGFβ1水平升高,差异有显著性意义(P<0．01)。糖尿病三组之间比较,PDR组血清TGFβ1水平高于背景型DR组;背景型DR组血清TGFβ1水平高于NODR组,三组之间差异均有显著性意义(P<0．05)。苯那普利治疗后背景型DR患者血清TGFβ1水平及UAER降低,与治疗前比较,差异均有显著性意义(P<0．05)。福辛普利治疗前后DR眼底的变化与药物对照组比较,无显著性差异(P>0．05)。结论DR患者血清TGFβ1水平显著升高,且随病变进展进一步升高,TGFβ1可能在DR发病及其进展中发挥重要作用。福辛普利通过抑制背景型DR患者产生TGFβ1,从而发挥对视网膜可能的保护用,但短期内观察眼底的病变无明显改善。     

卡托普利对早期糖尿病视网膜病变的防治效果

目的探讨卡托普利对早期糖尿病视网膜病变(diabetic retinopathy,DR)的预防及治疗作用,寻求延缓其发生发展的有效方法。方法选取2008年8月至2009年6月就诊于我院的2型糖尿病患者122例。随机分为卡托普利治疗组52例52眼,健康教育对照组70例70眼。随访18个月,比较两组的疗效及各项检查指标。结果卡托普利治疗组31眼有效(59.62%),21眼无效;健康教育对照组25眼有效(35.71%),45眼无效,差异有统计学意义(P<0.01)。随访18个月后,治疗组与对照组相比糖化血红蛋白、收缩压、舒张压无统计学差异(P>0.05),而血肌酐显著低于对照组,2组比较差异有显著统计学意义(P<0.01)。结论卡托普利可以明显延缓早期DR的发生和发展,提示血管紧张素转换酶抑制剂类药物可能成为预防和治疗早期DR的有效手段之一。     

卡托普利防治糖尿病小鼠视网膜病变的实验研究

目的:探讨卡托普利对糖尿病视网膜病变发生的防治作用。方法:应用免疫组织化学方法和计算机图象分析技术对糖尿病小鼠未治疗组和卡托普利治疗组视网膜组织AngII和VEGF进行免疫组织化学测定和半定量分析。结果:AngII和VEGF在两组小鼠视网膜神经节细胞和血管内皮细胞均为阳性表达,而在正常对照组两者均为阴性表达。与糖尿病未治疗组相比,卡托普利治疗组的AngII和VEGF的平均灰度值明显增加,而面密度值明显降低,说明治疗组的免疫信号降低,阳性表达细胞数减少。结论:卡托普利可降低糖尿病小鼠视网膜组织AngII和VEGF的阳性表达,推测其对糖尿病视网膜病变具有一定的保护作用。     

肝X受体激动剂TO901317对糖尿病视网膜病变大鼠视网膜的保护作用

目的 探讨肝X受体激动剂TO901317对糖尿病视网膜病变(DR)大鼠视网膜的保护作用.方法 取24只健康SPF级SD大鼠,随机分为正常组、模型组、TO901317组,每组各8只.正常组大鼠不做任何处理;模型组、TO901317组大鼠在禁食24 h后测量空腹血糖浓度,腹腔内注射链脲佐菌素60 mg·kg-1,1周后采尾...     

糖尿病性视网膜病变患者VEGF与微血管损伤的相关性

目的：探讨糖尿病视网膜病变(diabetic retinopathy, DR)患者血管内皮生长因子(vascular endothelial growth factor, VEGF)水平与微血管损伤程度的相关性。

方法：回顾性分析本院收治的糖尿病患者71例,根据有无DR及病变程度分为三组：单纯糖尿病组(n=31)、单纯型DR组(n=22)、增殖型DR组(n=18),比较各组微血管病变发生率。同时,取患者空腹肘静脉血,采用ELISA试剂盒测定血清VEGF水平,采用流式细胞仪检测内皮细胞(ECs)、内皮祖细胞(EPCs)、循环祖细胞(CPCs)计数。

结果：各组糖尿病肾病和糖尿病神经病变发生率有明显差异,增殖型DR组高于单纯型DR组和单纯糖尿病组,差异有统计学意义(P<0.05)。各组VEGF水平有明显差异,增殖型DR组高于单纯型DR组和单纯糖尿病组,单纯型DR组高于单纯糖尿病组; 合并糖尿病肾病及糖尿病神经病变者VEGF水平高于非合并者,差异均有统计学意义(P<0.05)。各组之间ECs、EPCs、CPCs水平有明显差异,增殖型DR组ECs高于单纯型DR组和单纯糖尿病组,单纯型DR组高于单纯糖尿病组; 增殖型DR组EPCs、CPCs水平低于单纯型DR组和单纯糖尿病组,单纯型DR组低于单纯糖尿病组,差异有统计学意义(P<0.01)。增殖型DR患者的VEGF水平与ECs水平呈正相关性(P<0.01),与EPCs、CPCs水平呈负相关性(P<0.01)。

结论：VEGF在糖尿病视网膜病变,尤其是增殖型糖尿病视网膜病变的临床诊断和医疗中,有重要意义。     

结缔组织生长因子在糖尿病视网膜病变中的研究进展

结缔组织生长因子(connective tissue growth factor,CTGF)是即刻早期基因CCN家族的成员之一.CTGF与多种细胞因子相互作用,可调节细胞间的黏附迁移、促进有丝分裂的发生、细胞活化和参与血管的生成.CTGF有望成为基因诊断和治疗糖尿病视网膜病变的有效靶标.     

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。     

瘦素、血管内皮生长因子与糖尿病视网膜病变

瘦素为肥胖基因的产物，这种脂肪来源的激素已被证明有多种生物学效应，其中促进新生血管形成的作用日益受到人们的关注。血管内皮生长因子（VEGF）是目前已知的最强的促进新生血管形成的细胞因子，瘦素通过上调VEGF的表达在糖尿病视网膜病变（DR）中发挥重要作用。本文就瘦素和VEGF的生物学特征、与DR的关系及其病理机制等作一综述。     

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。     

Pathogenesis of diabetic retinopathy and the renin-angiotensin system.

Despite the beneficial effects of good glycaemic control, loss of vision because of diabetic retinopathy (DR) still occurs. Recent studies have suggested that hypertension is a risk factor for the development and progression of DR and that blood pressure reduction can delay the progression of retinopathy. The renin-angiotensin system is activated by chronic hyperglycaemia, and the vitreous fluid level of angiotensin II (AII) is elevated in patients with proliferative diabetic retinopathy and diabetic macular oedema. AII increases vascular permeability and promotes neovascularization. It has been suggested that an autocrine-paracrine relationship may exist between AII and vascular endothelial growth factor in the ocular tissues. Accordingly, angiotensin-converting enzyme inhibitors or AII Type 1 (AT1) receptor blockers may be useful therapeutic agents for preventing the progression of DR.     

Beneficial effects of protocatechuic acid on diabetic retinopathy in streptozocin-induced diabetic rats

AIM: To determine the effects of protocatechuic acid (PCA) on streptozocin-induced diabetic retinopathy (DR) in rats.METHODS: Wistar rats were given a 50 mg/kg intraperitoneal injection of streptozocin to induce diabetes. Animals were assigned randomly one of four groups (8 rats per group): control, diabetic, diabetic plus PCA (25 mg/kg•d), and diabetic plus PCA (50 mg/kg•d). After inducing diabetes, treatments were started one week later and continued for eight weeks. After the experiment, the rats were sacrificed, and their retinas were taken for biochemical and molecular analysis.RESULTS: PCA administration diminished the blood glucose and glycated haemoglobin levels relative to the diabetic group. In diabetic rats, PCA lowered elevated levels of advanced glycosylated end products (AGEs) and receptor for AGEs (RAGE). In the retina of diabetic rats, PCA effectively decreased inflammatory cytokine, nuclear factor-κB, tumour necrosis factor-α, interleukin-1β, and vascular endothelial growth factor, and increased antioxidant markers glutathione, superoxide dismutase, and catalase.CONCLUSION: The protective benefits of PCA against DR may be attributable to its suppression of the AGEs and RAGE and its antioxidant and anti-inflammatory properties.     

糖尿病视网膜病变药物治疗的研究进展

随着糖尿病视网膜病变(diabetic retinopathy,DR)发病机制的深入研究,目前对DR的药物治疗取得了一定的成果,包括糖皮质激素、抗血管内皮细胞生长因子、抗血小板源性生长因子、非甾体类消炎药以及改善视神经功能的药物.目前治疗糖尿病黄斑水肿,玻璃体注药治疗特别是抗血管内皮细胞生长因子药物已逐渐推广.     

VEGF localisation in diabetic retinopathy

AIM—To determine the staining pattern of vascular endothelial growth factor (VEGF) at different stages of diabetic retinopathy (including post-laser photocoagulation) and to compare staining in excised fibrovascular and fibrocellular (non-diabetic) preretinal membranes.
METHODS—Immunohistochemical localisation of VEGF, using antibodies raised against VEGF₁₆₅ and VEGF_121,165,189, was carried out on specimens of normal human retina (n=15), diabetic retinas ((a) with no overt retinopathy (n=19), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n=6), (c) with active proliferative retinopathy (n=6), (d) with no residual proliferative retinopathy after photocoagulation therapy (n=15)), excised diabetic fibrovascular membranes (n=19), and non-diabetic fibrocellular membranes (n=7). The degree and pattern of immunostaining was recorded.
RESULTS—In general, VEGF was absent from the majority of normal retinas. VEGF staining was apparent in most diabetic tissues but the staining pattern was dependent on both the specificity of the antibody used and the category of tissue. Staining with the VEGF₁₆₅ antibody was generally confined to endothelial cells and perivascular regions while the VEGF_121,165,189 antibody was also associated with extravascular components of the inner retina. Intensity of immunostaining of diabetic eyes was dependent on the severity of retinopathy being least in diabetics with no overt retinopathy and greatest in retinas with proliferative retinopathy. Interestingly, the intensity of immunostaining in diabetic retinas which had undergone laser surgery for proliferative retinopathy was reduced to basal levels. Moderate to intense immunostaining was observed in all fibrovascular and fibrocellular membranes examined.
CONCLUSIONS—This study supports a circumstantial role for VEGF in the pathogenesis of both the preclinical and proliferative stages of diabetic retinopathy.

Keywords: vascular endothelial growth factor; VEGF; diabetes; diabetic retinopathy     

抗血管内皮生长因子药物治疗糖尿病视网膜病变的研究现状

糖尿病可引起眼内血管内皮生长因子（vascularendothelialgrowthfactor,VEGF）水平病理性升高,导致眼内新生血管形成、黄斑水肿的发生。抗VEGF药物最早被用于湿性年龄相关性黄斑变性,现也被试验性地用于糖尿病视网膜病变（diabeticretinopathy,DR）。VEGFl65选择性拮抗剂Pe—gaptanib与VEGF—A单抗Ranibizumab被批准玻璃体内注射,且对DR有较好的疗效;VEGF．A全长抗体Bevacizumab被标示外用于玻璃体内注射治疗DR,也能达到较好的效果;重组融合蛋白Aflibercept针对DR的疗效也得到一些试验的支持。玻璃体内注射抗VEGF药物治疗DR已被证实短期有效且安全,但其长期的疗效与安全性有待更多的大规模临床试验来验证。     

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.