糖基化终末产物对冠心病患者支架术后再狭窄的影响

目的探讨糖基化终末产物(AGEs)对经皮冠状动脉介入(PCI)术后1年再狭窄率的影响。方法择期PCI治疗的患者依据AGEs水平的平均值分成低AGEs和高AGEs组,记录介入血管支数,支架数目、再狭窄发生率。结果两组基础状态包括性别、年龄、高血压病史等均无统计学差异(P0.05),两组间介入血管支数,支架数目无统计学差异(P0.05)。两组间PCI术后再狭窄发生率存在明显差异。结论 AGEs增加冠心病患者PCI术后1年再狭窄发生率。     

阻塞性睡眠呼吸暂停低通气综合征患者血清糖基化终末产物的变化

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是心血管疾病、脑血管意外、糖尿病、代谢综合征等多种全身疾患的独立因素。晚期糖基化终末产物（advanced glycation end products，AGE）是指蛋白质、脂质或核酸等大分子在没有酶参与的条件下，自发地与葡萄糖或其他还原单糖发生非酶糖基化反应，生成的一组产物总称。我们通过观察OSAHS患者血清中AGE水平的变化，初步探讨血清AGE与OSAHS的关系。     

高级糖基化终末产物的检测及其临床意义

高级糖基化终末产物(AGEs)是蛋白质、脂类、核酸等生物大分子物质发生非酶糖基化反应的产物。近期大量研究证明，AGEs在糖尿病并发症^[1]、尿毒症^[2]、阿尔次海默病^[3]、白内障^[4]、脊髓侧索硬化症^[5]等疾病和衰老的发生发展过程中具有重要作用，因此检测血清和组织中AGEs的浓度对多种疾病的诊断、治疗及     

冠心病患者外周血单核细胞表面晚期糖基化终末产物受体水平的表达

目的探讨外周血单核细胞表面晚期糖基化终末产物受体(RAGE)的表达水平与冠心病患者临床表现及冠状动脉病变严重程度的关系,并评估其对冠心病患者风险的预测价值.方法 选择因胸痛住院并行冠状动脉造影的患者80例,据其不同临床表现、冠状动脉病变的Gensini积分、病变血管支数进行相应分组,采用流式细胞学方法测定外周血单核细胞表面RAGE水平.结果 急性心肌梗死组、不稳定型心绞痛组外周血单核细胞表面RAGE表达水平均高于稳定型心绞痛组和对照组(P＜0.01).RAGE水平与高敏C反应蛋白水平呈正相关(r=0.476,P=0.01);多支病变组和两支病变组外周血单核细胞表面RAGE表达水平高于单支病变组(P＜0.05);多支病变组RAGE水平高于两支病变组(P＜0.05);根据冠状动脉造影Gensini评分分为三组,三组间外周血单核细胞表面RAGE水平逐渐升高,且各组间差异均具有统计学差异.外周血单核细胞表面RAGE水平与冠状动脉造影评分之间呈正相关(r＝0.376,P=0.007);采用Logistic回归法分析高水平的外周血单核细胞表面RAGE水平是冠心痛患者发生急性冠状动脉综合征的独立危险因素(OR=1.180,P=0.02).结论 冠心病患者外周血单核细胞表面RAGE表达水平明显增加,且随着临床表现严重程度的增加呈逐渐升高趋势,对冠心病患者的临床表现有预测价值.外周血单核细胞RAGE水平与冠状动脉病变狭窄程度相关,对冠状动脉病变严重程度有一定的预测价值.高水平外周血单核细胞RAGE的表达是冠心痛患者临床表现严重程度的独立危险因素.     

糖基化终末产物及其受体在胃肠道中的分布

目的:研究糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在胃肠道中的分布,为进一步探索其在慢性糖尿病胃肠功能紊乱中的作用奠定基础.方法:分别对成年Wistar大鼠食管、胃、十二指肠、空肠、回肠、结肠及直肠组织进行AGE及RAGE免疫组织化学染色.结果:(1)食管:AGE及RAGE主要分布在横纹肌的肌细胞及黏膜的鳞状上皮细胞;(2)胃:AGE在壁细胞为强阳性.RAGE在主细胞、肥大细胞、神经细胞为强阳性,在壁细胞为中等强度阳性,在表面黏液细胞为弱阳性;(3)小肠:AGE及RAGE在绒毛及固有层上皮细胞为阳性或强阳性.RAGE在肠道的神经细胞亦为强阳性;(4)结肠及直肠:AGE及RAGE在黏膜上皮细胞为弱阳性,RAGE在神经细胞为强阳性.结论:AGE及RAGE广泛分布于肠道上皮细胞及食管的横纹肌细胞,AGE亦分布于胃的壁细胞,RAGE亦分布于胃的壁细胞、主细胞、表面黏液细胞、肥大细胞及胃肠道的神经细胞.     

晚期糖基化终末产物受体及其配体在骨代谢疾病中作用的研究进展

晚期糖基化终末产物受体(RAGE)是具有多种配体的免疫球蛋白超家族成员,参与多种疾病的发病机制,包括神经退行性疾病阿尔茨海默病、糖尿病并发症以及多种与衰老、炎症相关的疾病,在调节先天免疫反应中起着关键作用.RAGE及其配体不仅是多种炎症反应的重要细胞因子,而且在骨髓间充质干细胞、成骨细胞及破骨细胞均表达RAGE.近年来...     

晚期糖基化终末产物与骨质疏松症

骨质疏松的主要表现是低骨量和骨组织微结构退变,其发生的本质在于骨再造过程紊乱即骨吸收超过骨形成。骨吸收与骨形成分别与破骨细胞和成骨细胞的活动直接相关。目前研究发现众多激素、生长因子和细胞因子等参与均衡这两类细胞的数量和活性,影响骨代谢平衡,晚期糖基化终末产物也是目前其中研究较为广泛的因子之一。晚期糖基化终末产物随着年龄增长在体内积聚增多,通过直接或间接的作用导致骨代谢的失衡,出现骨质疏松。     

慢阻肺急性加重期患者血浆晚期糖基化终末产物和sRAGE研究

目的研究分析慢性阻塞性肺疾病(慢阻肺)患者血浆中晚期糖基化终末产物(AGEs)和可溶性糖基化终末产物受体(sRAGE)的水平及与慢阻肺患者肺功能的关系。方法选取河北省承德县医院收治的120例慢阻肺患者(慢阻肺组)、50例健康人群(对照组),分别检测两组的血浆AGEs、sRAGE及肺功能等指标。结果慢阻肺组患者的血浆中AGEs(36.25±2.98)ug/m L显著的高于对照组的(28.94±2.31)ug/m L,sRAGE为(338.41±194.26)pg/m L显著的低于对照组的(871.50±226.49)pg/m L且差异均具有统计学意义(P0.05)。慢阻肺组患者血浆AGEs与患者的FEV1%呈显著的负相关关系(r=-0.594,P=0.0000.001);慢阻肺组患者血浆sRAGE与患者的FEV1%呈显著的正相关关系(r=0.552,P=0.0000.001)。结论慢阻肺患者血浆中AGEs、sRAGE水平发生显著的改变,AGEs与患者的肺功能呈负相关性、sRAGE与患者的肺功能呈正相关关系。     

糖基化终末产物对阿尔茨海默病的影响

本文综述了糖基化终末产物对神经胶质细胞和神经元细胞的影响,观察糖基化终末产物引起的神经胶质细胞和神经元细胞的变化,探讨糖基化终末产物引起阿尔茨海默病的可能性及其机理。以期能更好地预防和治疗阿尔茨海默病。     

糖基化终末产物与肝病

肝脏是糖基化终末产物的主要代谢部位,肝病时伴随的氧化应激、糖耐量损害以及肝肾功能降低导致糖基化终末产物增加,而糖基化终末产物可通过促进氧应激/脂质过氧化、炎症反应以及纤维化等途径,加重肝脏损伤。     

冠心病合并糖尿病患者替格瑞洛、氯吡格雷的抗栓效能评价及糖基化终末产物价值分析

目的评估冠心病合并糖尿病患者替格瑞洛、氯吡格雷的抗栓效能并进一步分析血清糖基化终末产物在治疗过程中的作用。方法入选2014年10月至2017年2月期间在江苏大学附属医院心内科行PCI术治疗的冠心病合并糖尿病患者120例。随机分为两组,分别予以氯吡格雷(n=60)及替格瑞洛(n=60)治疗。双联抗血小板治疗前及治疗1周后采用流式细胞术检测血小板聚集率,血栓弹力图检测花生四烯酸(AA)和二磷酸腺苷(ADP)途径诱导的血小板抑制率,比较两组抗血小板治疗的效果。ELISA法检测两组血清糖基化终末产物(AGE)水平。治疗6个月后通过随访观察两组患者出血事件及缺血事件发生情况。结果两组患者治疗1周后替格瑞洛组血小板聚集率显著低于氯吡格雷组14.09%[(35.92±7.57)%比(41.81±9.56)%,P0.05];两组间经AA途径诱导的血小板抑制率差异无显著性(P0.05),但经ADP途径诱导的血小板抑制率替格瑞洛组是氯吡格雷组的1.22倍[(65.73±11.69)%比(53.67±8.75)%,P0.05)]。治疗前两组患者血清AGE水平差异无显著性,治疗后1周替格瑞洛组血清AGE水平低于氯吡格雷组,差异有统计学意义[(18.71±3.14)mg/L比(25.71±4.01)mg/L,P0.05)]。Pearson相关分析表明血清AGE水平与血小板聚集率正相关(r=0.87,P0.001),与血小板抑制率负相关(r=-0.95,P0.001)。治疗6个月后随访显示两组间出血事件差异无显著性;但在缺血事件方面,替格瑞洛组发生总缺血事件的概率要显著低于氯吡格雷组(8.33%比18.33%,P0.05)。结论替格瑞洛较氯吡格雷能明显降低PCI术后1周血小板聚集率,减少半年缺血事件的发生率,血清AGE水平可能是这一过程的关键节点。     

Role of advanced glycation end products in cardiovascular disease

Advanced glycation end products(AGEs) are produced through the non enzymatic glycation and oxidation of proteins,lipids and nucleic acids.Enhanced formation of AGEs occurs particularly in conditions associated with hyperglycaemia such as diabetes mellitus(DM).AGEs are believed to have a key role in the development and progression of cardiovascular disease in patients with DM through the modif ication of the structure,function and mechanical properties of tissues through crosslinking intracellular as well as extracellular matrix proteins and through modulating cellular processes through binding to cell surface receptors [receptor for AGEs(RAGE)].A number of studies have shown a correlation between serum AGE levels and the development and severity of heart failure(HF).Moreover,some studies have suggested that therapies targeted against AGEs may have therapeutic potential in patients with HF.The purpose of this review is to discuss the role of AGEs in cardiovascular disease and in particular in heart failure,focussing on both cellular mechanisms of action as well as highlighting how targeting AGEs may represent a novel therapeutic strategy in the treatment of HF.     

糖基化终末产物与冠心病相关性的临床观察

目的探讨糖基化终末产物与冠心病的相关性。方法分别检测正常对照组、冠心病组、糖尿病组及冠心病合并糖尿病组的血清糖基化终末产物、糖化血红蛋白,并进行相关分析。结果各观察组血清糖基化终末产物均较正常对照组升高,且各组间的差异有显著性(P<0.05),糖基化终末产物与糖化血红蛋白呈正相关(r=0.738,P=0.000)。结论血清糖基化终末产物与冠心病具有相关性,并且是糖尿病心血管合并症的相关危险因素。     

Increased serum concentrations of advanced glycation end products: a marker of coronary artery disease activity in type 2 diabetic patients

OBJECTIVE—To assess whether the concentrations of serum advanced glycation end products (AGE) in diabetic patients with obstructive coronary artery disease differ from those in type 2 diabetic patients without obstructive coronary artery disease.
DESIGN—Serum AGE concentrations were measured in type 2 diabetic patients and in non-diabetic patients, both with and without obstructive coronary artery disease, and the relation between these values and coronary disease severity was evaluated.
RESULTS—Mean (SD) serum AGE concentrations were higher (p < 0.0125) in type 2 diabetic patients with obstructive coronary artery disease (5.5 (2.5) mU/ml, n = 30) than in patients without obstructive coronary artery disease (2.8 (0.5) mU/ml, n = 12), and higher than in non-diabetic patients with (3.4 (1.0) mU/ml, n = 28) and without (3.2 (0.4) mU/ml, n = 13) obstructive coronary artery disease. Serum AGE was associated with the degree of coronary arteriosclerosis in type 2 diabetic patients with obstructive coronary artery disease (single vessel: n = 13, 3.4 (0.9) mU/m; two vessel: n = 6, 5.7 (1.6) mU/m; three vessel: n = 11, 7.2 (2.5) mU/ml). Serum AGE was positively correlated with serum mean four year HbA_1C (r = 0.46, p < 0.01), but not with recent serum HbA_1C (r = 0.24). The four groups did not differ in the other coronary risk factors.
CONCLUSIONS—Serum AGE concentrations may be associated with long term poor glycaemic control and reflect the severity of coronary arteriosclerosis in type 2 diabetic patients.


Keywords: advanced glycation end products; non-insulin dependent diabetes; coronary artery disease     

Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in type 2 diabetes

Aims/hypothesis Activation of the receptor for advanced glycation end products (RAGE, also known as AGE-specific receptor [AGER]) has been implicated in the development of diabetic vascular complications. Blockade of RAGE using a soluble form of the receptor (sRAGE) suppressed vascular hyperpermeability and atherosclerosis in animal models. Since little is known about the regulation of endogenous sRAGE levels, we determined whether serum sRAGE is influenced by circulating AGEs and the severity of nephropathy in type 2 diabetic patients.Materials and methods We recruited 150 healthy control and 318 diabetic subjects. Diabetic subjects were subdivided into those with proteinuria, microalbuminuria or normoalbuminuria. Serum sRAGE was assayed by ELISA and serum AGEs by competitive ELISA using a polyclonal rabbit antiserum raised against AGE-RNase.Results Diabetic subjects had higher sRAGE (1,029.5 pg/ml [766.1–1,423.0] interquartile range vs 1,002.6 [726.5–1,345.3], p<0.05) and AGEs (4.07±1.13, SD, unit/ml vs 3.39±1.05, p<0.01) than controls. Proteinuric subjects had the highest sRAGE levels and there was a significant trend between the severity of nephropathy and sRAGE (p=0.01). In diabetic subjects, serum log(sRAGE) correlated with AGEs (r=0.27, p<0.001), log(plasma creatinine) (r=0.31, p<0.001), log(urine AER) (r=0.24, p<0.01) and log(triglycerides) (r=0.15, p<0.01). On stepwise linear regression analysis, AGEs and creatinine levels were the main independent determinants of sRAGE concentration.Conclusions/interpretation Serum sRAGE levels and circulating AGEs are associated with the severity of nephropathy in type 2 diabetic patients. Prospective studies are required to determine whether endogenous sRAGE potentially influences the development of diabetic vascular complications.     

The different roles for the advanced glycation end products axis in heart failure and acute coronary syndrome settings

AimsThis work aimed to compare the behavior of the advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in two cohorts of patients: those with heart failure (HF) and acute coronary syndrome (ACS).Methods and resultsA unicentric observational clinical study was performed in 102 patients with ACS and 102 patients with chronic HF matched by age and gender. At inclusion, fluorescent AGEs were measured by quantitative fluorescence spectroscopy of plasma, and total sRAGE and endogenous secretory RAGE (esRAGE) levels were determined by enzyme-linked immunosorbent assay kits. A 5-year follow-up period was established for recording cardiac death (primary endpoint) and the incidence of non-fatal myocardial infarction or HF readmission (secondary endpoints). Higher glycation parameters were observed in HF patients, whereas no differences in sRAGE forms were found between HF and ACS cohorts, except for cRAGE, which was higher in HF. Associations between glycation parameters and sRAGE forms were observed in HF, but not in ACS. Differences were also evidenced in the long-term prognosis of each cohort: esRAGE showed an independent prognostic value for cardiac death or non-fatal cardiovascular events in HF, but none of the AGE–RAGE variables were predictors in ACS.ConclusionsA different role for the AGE–RAGE axis was observed in HF and ACS. All the sRAGE forms were directly related with glycation parameters in HF, but not in ACS. The independent value of the sRAGE forms on each cardiovascular disease was supported by esRAGE being an independent predictor of bad long-term prognosis only for HF.     

高级糖基化终末产物的合成及其与疾病的关系

高级糖基化终末产物(advanced glycation end products,AGEs)是由蛋白或者脂质暴露于还原糖中而形成的一组复杂且具有异质性的物质.该物质可通过内源性或外源性途径形成,大体可分为6种.AGEs可在不同种类的细胞内累积,影响细胞内及细胞外的结构和功能,同时它还可以通过和细胞表面的受体作用,通过信号传导,引发一系列的病理生理过程.AGEs沉积在细胞内,影响细胞功能,导致糖尿病血管并发症的发生.AGEs还与各种肿瘤的生物学特性相关,它可以修饰热休克蛋白27或者与AGEs受体相结合来影响肿瘤细胞的生长和浸润.AGEs的抑制物,如OPB-9195,可抑制这一系列病理生理过程.     

Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis

BACKGROUND AND AIM: Advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate in diabetes, play important roles in the pathogenesis of diabetic vascular complications. Recently, AGE have also been found to be involved in insulin resistance. Although non-alcoholic steatohepatitis (NASH) is generally considered a hepatic manifestation of insulin resistance, there are no reports showing the link of AGE to NASH. The aim of this study was to evaluate the clinical significance of AGE in patients with NASH. METHODS: Glyceraldehyde-derived AGE levels were assayed from serum obtained from 106 patients: 66 with NASH, 10 with simple steatosis, and 30 controls. RESULTS: Serum glyceraldehyde-derived AGE levels (U/mL) were significantly elevated in NASH patients (9.78 +/- 3.73) compared with simple steatosis (7.17 +/- 2.28, P = 0.018) or healthy controls (6.96 +/- 2.36, P = 0.003). Moreover, these were inversely correlated with adiponectin, an adipocytokine with insulin-sensitizing and anti-inflammatory properties. In addition, immunohistochemistry of glyceraldehyde-derived AGE showed intense staining in the livers of NASH patients. CONCLUSION: The present data suggest that the sustained increase of glyceraldehyde-derived AGE could at least in part contribute to the pathogenesis of NASH. The serum glyceraldehyde-derived AGE level may be a useful biomarker for discriminating NASH from simple steatosis.