蛋白质组学及其在糖尿病肾病中的应用

蛋白质组学是一门以蛋白质组为研究对象，在蛋白质水平上对疾病机理、细胞模式、功能联系等方面进行探索的科学。其核心技术有二维凝胶电泳、质谱分析、蛋白质组信息学。其在探讨糖尿病肾病的发病机制及早期诊断中的应用前景十分广阔。     

蛋白质组学及其在糖尿病肾病中的应用

蛋白质组学是一门以蛋白质组为研究对象 ,在蛋白质水平上对疾病机理、细胞模式、功能联系等方面进行探索的科学。其核心技术有二维凝胶电泳、质谱分析、蛋白质组信息学。其在探讨糖尿病肾病的发病机制及早期诊断中的应用前景十分广阔。     

糖尿病肾病研究进展

糖尿病肾病是糖尿病最严重的微血管并发症。近10年来,糖尿病肾病患者快速增长,已成为危害人类健康的公共卫生疾病。目前在欧美等发达国家,DN约占终末期肾病(ESRD)的50%,已成为尿毒症的首位原发病;在我国约占25%～40%,是患者血液透析的重要原因。因此,及时发现与防治DN,对于延缓病情进展、提高患者生活质量意义重大。     

糖尿病肾病发病机制的研究进展

糖尿病肾病( diabetic nephropathy,DN)是糖尿病(diabetes mellitus,DM)最主要的微血管并发症,近年来,DN已成为世界范围内导致终末期肾病(end stage renal disease,ESRD)的首位病因.在我国,DN发病率也逐年上升,成为仅次于慢性肾炎引起ESRD的第二大原因,严重地影响了人们的健康水平.DN患者体内复杂的代谢紊乱、肾脏血流动力学的改变及一些细胞因子的产生使其比其他肾脏病的治疗更加棘手,因此,进一步研究DN的发病机制,制定更有效的防治措施,是当前糖尿病和肾脏病领域十分急迫的课题.     

糖尿病肾病发病机制的研究进展

糖尿病肾病(DN)是糖尿病(DM)的严重微血管并发症之一。以基底膜(GBM)增厚、系膜区扩张、胞外基质堆积为病理特征,是引起终末期肾衰的重要原因,也是DM病人的主要死亡原因之一。DN的发生与肾小球的血流动力学改变、多元醇代谢途径异常、蛋白非酶糖化和大分子糖化终末产物(AGEs)的生成、细胞因子的异常表达及脂代谢紊乱等因素密切相关。     

Nephrin与糖尿病肾病的研究进展

nephrin是特异的表达于足细胞的一种蛋白,定位于足突细胞裂隙隔膜,是维持肾小球滤过屏障完整性的关键分子。糖尿病肾病患者存在该基因的异常或是mRNA表达的变化,使肾滤过膜结构与屏障功能完整性破坏,最终导致大量蛋白尿的产生。阻滞肾素-血管紧张素系统(RAS)可减轻nephrin表达的减少。     

Nephrin与糖尿病肾病的研究进展

nephrin是特异的表达于足细胞的一种蛋白，定位于足突细胞裂隙隔膜，是维持肾小球滤过屏障完整性的关键分子。糖尿病肾病患者存在该基因的异常或是mRNA表达的变化。使肾滤过膜结构与屏障功能完整性破坏，最终导致大量蛋白尿的产生。阻滞肾素一血管紧张素系统（RAS）可减轻nephrin表达的减少。     

糖尿病肾病药物治疗研究进展

糖尿病已经成为全世界范围内重要的、日渐突出的健康问题。虽然目前已有多种治疗可减缓糖尿病肾病的发生和发展,新的治疗措施仍十分必要。随着对糖尿病肾病发病机制的深入了解,新的治疗措施不断涌现。本文简述了目前糖尿病肾病药物治疗方面的研究成果,包括已广泛应用的药物如RAAS阻滞剂、噻唑烷二酮类降糖药、降脂药等治疗糖尿病肾病的新理论依据及新药物,包括蛋白非酶糖基化阻滞剂、生长因子拮抗剂等。     

血管紧张素-Ⅰ转换酶基因多态性与糖尿病及糖尿病肾病的关系

目的　探讨血管紧张素Ⅰ转换酶基因（ＡＣＥ基因） 多态性与糖尿病及糖尿病肾病（ＤＮ） 的易感性之间的关系。方法　应用聚合酶链式反应（ＰＣＲ）方法扩增４８ 例正常人、７４ 例胰岛素依赖型糖尿病（ＩＤＤＭ） 患者（ 其中４０ 例不伴ＤＮ,３４ 例合并ＤＮ） 、１０２ 例非胰岛素依赖型糖尿病（ＮＩＤＤＭ） 患者（５７ 例不伴ＤＮ,４５ 例伴ＤＮ） 的ＡＣＥ基因上２８７ｂｐ 片断,根据插入（Ｉ） 或缺失（Ｄ） 来判断其多态性。结果　健康对照组与ＩＤＤＭ 及ＮＩＤＤＭ 组ＡＣＥ 等位基因、基因型均无显著性差异（ Ｐ＞０－０５）;在ＩＤＤＭ 组中,Ｄ等位基因及ＤＤ基因型在伴ＤＮ亚组中显著升高;在ＮＩＤＤＭ 组中,与不伴ＤＮ者比较,伴ＤＮ者其Ｉ等位基因、ＩＩ基因型频率明显为低。结论ＡＣＥ 基因多态性与糖尿病易感性无关,与ＤＮ密切相关。     

糖尿病肾病现状与挑战

糖尿病肾病(DN)是糖尿病的严重并发症,近年来DN发病率呈不断上升趋势,是发达国家终末期肾病(ESRD)的主要病因,也是我国中老年人ESRD的主要病因。提高DN的认识与管理具有重大意义。本文对近年来国内外有关DN的流行病学、临床与病理诊断、易感基因、生物标志物及其治疗等方面的最新进展进行述评,同时对DN治疗现状与面临的挑战提出新的认识,以引起同行重视。     

糖尿病肾病与非糖尿病性肾脏疾病的对比分析及其诊断概率回归方程的建立

目的 对比分析糖尿病肾病和糖尿病合并的非糖尿病性肾脏疾病的不同临床特征，探索两组疾病的临床鉴别诊断依据，建立糖尿病肾病诊断概率回归方程。方法肾活检前临床诊断为糖尿病肾病患者共110例，经肾活检后，按病理诊断分为两组：DN组(糖尿病肾病)60例，NDRD组(非糖尿病性肾脏疾病)50例。对两组资料进行统计分析。结果单因素及多因素回归分析显示，糖尿病患病时间、收缩压、糖化血红蛋白、有无血尿和视网膜病变与糖尿病肾病诊断相关。由所得参数建立糖尿病肾病诊断概率回归方程。经检验，方程判断糖尿病肾病灵敏度为90%，特异度为92％，阳性预测值为93％，阴性预测值为88％，准确率为91％。结论2型糖尿病伴肾脏损害并不一定是糖尿病肾病，相当部分是非糖尿病性肾脏疾病，回归方程的建立可为临床鉴别诊断提供帮助。     

Association of genetic variants with diabetic nephropathy

Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, e NOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.     

Evolving spectrum of diabetic nephropathy

Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy(DN), which classically presents with proteinuria followed by a progressive decrease in renal function.However, an increasing proportion of DN patients have a decline in kidney function and vascular complications without proteinuria, known as nonproteinuric DN(NP-DN). Despite the increased incidence of NP-DN, few clinical or experimental studies have thoroughly investigated the pathophysiological mechanisms and targeted treatment for this form of DN. In this review, we will examine the differences between conventional DN and NP-DN and consider potential pathophysiological mechanisms, diagnostic markers, and treatment for both DN and NP-DN. The investigation of the pathophysiology of NP-DN should provide additional insight into the cardiovascular factors influencing renal function and disease and provide novel treatments for the vascular complications seen in diabetic patients.     

糖尿病肾病与糖尿病视网膜病变的相关性研究进展

糖尿病肾病(DN)和糖尿病视网膜病变(DR)均是糖尿病的微血管病变，是目前成人终末期肾病(ESRD)和致盲的重要原因，两者在发生、发展过程中具有一定平行性，又存在不平行性。DN和DR可预测彼此的发生、发展，但目前对于两者之间的关系尚未明确。因此，本文就DN与DR之间的相关性的研究进展作一综述，为临床诊断治疗提供帮助。     

Relationship between E - cadherin and diabetic nephropathy

Objective To identify novel biomarker for diabetic nephropathy (DN) by urinary proteomic methods, and to detect the expression of E-cadherin in urine and renal tissue of patients with DN. Methods Urine samples were collected from 12 cases of type 1 diabetic nephropathy patients (T1DN), 12 cases of type 2 diabetic nephropathy patients (T2DN), 12 cases of nephritic syndrome patients (NS), and 12 cases of healthy Controls. Comparative proteomic approach of two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) were employed to identify DN-related biomarker in urine samples. The differential expression of the identified biomarker in urine samples and renal biopsy specimens were detected by Western blotting and immunohistochemistry method. Results E-cadherin was identified by 2DE/MS, which was significantly up-regulated in T1DN and T2DN groups (all P＜ 0.01). Western blotting confirmed the expression of E-cadherin was significantly higher in T1DN and T2DN groups than in NS and Control groups (all P＜0.01). Immunohistochemical stain showed E-cadherin was mainly expressed in the membrane and cytoplasm of renal tubular epithelial cell, and its expression was markedly decreased in DN kidneys compared with healthy Controls (P＜0.05). Conclusions E-cadherin is identified as a novel DN-related biomarker, which is specifically increased in urine of DN patients.     

表观遗传修饰在糖尿病肾病发病机制中的作用研究进展

"代谢记忆"现象是导致糖尿病并发症发病率持续增高的重要原因,其分子机制的研究主要聚焦在表观遗传修饰。表观遗传修饰在糖尿病肾病的纤维化、炎症、氧化应激、糖代谢及脂代谢紊乱等发病机制中有重要的作用。本文就该机制做一综述,并为进一步的分子研究、诊断及治疗提供新思路。     

大黄酸对2型糖尿病肾病大鼠疗效观察

目的：观察大黄酸防治2型糖尿病肾病的作用。方法：以高糖高脂饮食联合低剂量链脲佐菌素（STZ）注射方法诱导出2型糖尿病肾病大鼠模型后，分模型组、预防组和治疗组，后2组分别在STZ注射后1周和1个月后给予大黄酸100mg/kg剂量灌胃，每日1次，连续6个月，在不同时间进行形态学和有关生化指标的观察。结果：大黄酸预防给药和治疗后的观察结果显示，大黄酸明显降低糖尿病大鼠的24h尿蛋白排泄，改善肾重指数。肾脏组织病理学显示，大黄酸处理后的糖尿病大鼠肾小球和丝球体的面积明显减小，襻腔扩张减轻，系膜增生和细胞外基质减少。大鼠肾小球纤连蛋白沉积明显减弱。大黄酸也明显降低糖尿病大鼠的血脂水平。以上作用随着给药时间的延长，效果越来越明显。胰岛素抑制试验表明，在大黄酸预防给药和治疗6个月后，糖尿病大鼠的血浆稳态葡萄糖水平（SSPG）显著降低。以上结果比较，以预防组效果为佳。结论：大黄酸通过降低糖尿病大鼠的尿蛋白排泄、减轻肾脏肥大、改善胰岛素敏感性、降低血脂水平，有效地防治2型糖尿病肾病。