柚皮苷对糖尿病及其并发症作用机制的研究进展

柚皮苷主要存在于芸香科柑橘属植物柚、葡萄柚、酸橙及其变种的果皮及果实中,属于双氢黄酮类化合物。研究表明柚皮苷具有抗1型及2型糖尿病的药理作用,作用机制为通过抑制糖尿病相关的氧化应激损伤、炎症、糖代谢酶异常等方面,同时在一定程度上延缓糖尿病并发症（包括糖尿病心肌病、糖尿病肾病、糖尿病视网膜病变及糖尿病神经病变）的发生与发展。探讨柚皮苷对糖尿病及其并发症作用机制的研究进展,旨在为抗糖尿病新药研发提供依据。     

MicroRNAs as therapeutic targets for the treatment of diabetes mellitus and its complications

Introduction: Diabetes mellitus is a very common metabolic disorder affecting more than 400 million people worldwide. Currently available treatments permit to manage the disease but, in the long term, many patients develop severe micro- and macrovascular complications that decrease life quality and expectancy. Better therapeutic tools to prevent and treat diabetes are therefore urgently needed.

Areas covered: MicroRNAs are key regulators of gene expression and central players in a variety of physiological and pathological processes. This review summarizes the role of microRNAs in insulin-secreting cells and in insulin target tissues as well as their involvement in the development of diabetes and its long term complications.

Expert opinion: Because of their physicochemical properties and their capacity to regulate a wide range of physiopathological events, microRNAs are attractive therapeutic targets. There is accumulating evidence that approaches permitting to correct the level of specific microRNAs can successfully prevent or treat diabetes and its complications. Pharmacological tools that efficiently modulate the level of microRNAs are already available. However, before these tools can be allowed to integrate the arsenal for the treatment of diabetic patients, new innovative strategies will be needed to achieve selective delivery of these pharmacological principles to the appropriate target cells.     

同型半胱氨酸与糖尿病及其血管并发症的Meta分析

目的利用对大样本数据Meta分析的方法,对糖尿病及其合并并发症的糖尿病患者进行血浆同型半胱氨酸浓度的分析,探讨血浆同型半胱氨酸（homocysteine,Hcy）的水平与糖尿病血管并发症的关系。方法计算机检索中国期刊网全文数据库、中国生物医学文献数据库、万方数据库和维普数据库,并结合文献追溯的方法,收集2003～2010年关于血浆Hcy水平与糖尿病及其并发症的病例研究资料,以健康人群为对照组,糖尿病伴有血管并发症患者为病例组,采用采用RevMan4.2软件进行Meta分析。结果共纳入16个研究,包括1420例研究对象。Meta分析结果显示糖尿病合并血管并发症组Hcy水平明显高于正常对照组,其差异有统计学意义[WMD=9.12,95%CI（8.85,9.39）,P〈0.00001]。结论血浆Hcy的水平与糖尿病及其血管并发症之间的关系密切。     

Protective role of sulphoraphane against vascular complications in diabetes

Context Diabetes is a global health challenge. Although large prospective clinical trials have shown that intensive control of blood glucose or blood pressure reduces the risk for development and progression of vascular complications in diabetes, a substantial number of diabetic patients still experience renal failure and cardiovascular events, which could account for disabilities and high mortality rate in these subjects.

Objective Sulphoraphane is a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, such as broccoli, cabbage and Brussels sprouts, and an inducer of phase II antioxidant and detoxification enzymes with anticancer properties. We reviewed here the protective role of sulphoraphane against diabetic vascular complications.

Methods In this review, literature searches were undertaken in Medline and in CrossRef. Non-English language articles were excluded. Keywords [sulphoraphane and (diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic complications, vascular, cardiomyocytes, heart or glycation)] have been used to select the articles.

Results There is accumulating evidence that sulphoraphane exerts beneficial effects on vascular damage in both cell culture and diabetic animal models via antioxidative properties. Furthermore, we have recently found that sulphoraphane inhibits in vitro formation of advanced glycation end products (AGEs), suppresses the AGE-induced inflammatory reactions in rat aorta by reducing receptor for AGEs (RAGE) expression and decreases serum levels of AGEs in humans.

Conclusion These findings suggest that blockade of oxidative stress and/or the AGE-RAGE axis by sulphoraphane may be a novel therapeutic strategy for preventing vascular complications in diabetes.     

2型糖尿病各并发症及影响因素的临床分析

目的：总结2型糖尿病并发症的影响因素,为预防并发症提供依据。方法以366例2型糖尿病患者为对象,回顾性分析高血压、肾病、周围血管疾病、周围神经疾病等并发症的影响因素。结果年龄≥60岁是高血压、肾病、周围神经病变、周围血管病变及其他并发症发生的高危因素(χ2=25.971、21.941、8.099、17.712、7.668, P<0.01)。血糖≥6.1 mmol/L者易发生高血压(χ2=5.446, P<0.05)。脂代谢异常者易引发周围血管病变(χ2=13.455, P<0.01)。高血压易引发肾病、周围神经病变、周围血管病变及其他并发症(χ2=36.928、33.945、30.583、19.912, P<0.01)。结论对高龄、高血压、血糖过高和血脂代谢异常者,要加强治疗和干预,预防2型糖尿病各并发症发生。     

社区老年糖尿病人群血管并发症、合并症的发生情况及其影响因素

目的了解老年糖尿病(DM)人群中DM慢性并发症(微血管病变、大血管病变及神经病变等)和主要合并症(包括高血压、血脂代谢异常、肥胖等)的发生情况以及血管并发症的影响因素。方法采用横断面研究的方法,收集社区老年DM人群资料,并把DM血管并发症作为因变量,对其影响因素进行非条件logistic回归分析。结果老年DM慢性并发症以及高血压、血脂代谢紊乱、肥胖等合并症的发生率很高;经济水平较低社区、发病年限长、有DM家族史、医疗费支付有困难、空腹血糖控制不良、急性并发症、主要合并症是导致社区老年DM人群微血管并发症的主要独立因素;吸烟、嗜甜食、医疗费支付有困难、急性并发症、主要合并症是导致社区老年DM人群大血管并发症的主要独立因素。结论老年糖尿病人群糖尿病并发症及合并症的影响因素很多,这一方面说明其病情的复杂性,另一方面也为更好地控制其发生和发展及有效地降低致残率和致死率提供了综合控制的手段。     

Agents that block advanced glycation end product (AGE)-RAGE (receptor for AGEs)-oxidative stress system: a novel therapeutic strategy for diabetic vascular complications

Background: Diabetic vascular complications are leading causes of acquired blindness, end-stage renal failure, a variety of neuropathies, and accelerated atherosclerosis, which together could account for disabilities and high mortality rates in patients with diabetes. Since there is accumulating evidence that the advanced glycation end product (AGE)–RAGE (receptor for AGEs)–oxidative stress axis is involved in diabetic vascular complications, inhibition of the AGE–RAGE system may be a promising target for therapeutic intervention in these devastating disorders. Objective: In this review, we discuss several types of agent that may be able to inhibit the AGE–RAGE–oxidative stress system, and their therapeutic implications in vascular complications in diabetes. Methods: We have analyzed currently available scientific literature in the field of AGE–RAGE to create a comprehensive review on novel therapeutic agents for vascular complications in diabetes. Results/conclusion: Inhibition of AGE formation, blockade of the AGE–RAGE interaction, and suppression of RAGE expression or its downstream pathways may be novel therapeutic strategies for the treatment of vascular complications in diabetes.     

2型糖尿病合并脂代谢紊乱与血压、肥胖、并发症相关性的研究

目的：探讨2型糖尿病合并脂代谢紊乱与血压、肥胖、并发症的关系。方法：将155例2型糖尿病患者,按有无血脂异常分为高脂血症组和非高脂血症组,测定TG、LDL-C、HDL-C、TC、FPG、HbA1c、BP,计算BMI并进行统计学分析。结果：高脂血症组与非高脂血症组在收缩压、舒张压、BMI、载脂蛋白B（ApoB）等方面比较,差异有统计学意义（P均〈0.05）。在糖尿病肾病、糖尿病视网膜病变并发症方面,差异有统计学意义（P〈0.05）。结论：2型糖尿病合并脂代谢紊乱与血压、肥胖及糖尿病肾病、糖尿病视网膜病变有关。     

线粒体动力学与2型糖尿病和糖尿病并发症关系的研究进展

线粒体动力学即线粒体融合和分裂保持动态平衡的过程,线粒体的融合与分裂过程决定线粒体形态的可塑性。这种动态平衡的稳定是维持线粒体功能和机体功能的前提和基础,并且受多种化学酶及蛋白等因素调节。因线粒体为细胞能量代谢中心,故线粒体动力学与人类代谢性疾病的关联日益受到重视。近年来,大量研究表明,线粒体动力学失衡可以引起胰岛素抵抗和β细胞功能障碍,并且与糖尿病并发症发生密切相关。     

农村糖尿病患者健康教育知识掌握现状调查及其对慢性并发症发生率的影响

目的：了解本市农村糖尿病患者健康教育知识掌握现状及其对慢性并发症发生率的影响,唤起人们对糖尿病教育的重视。方法按参考文献设计糖尿病健康教育知识测评表,对150例本科住院的本市农村2型糖尿病患者进行问卷调查。在参与了问卷调查患者中选取病程在5~10年且病程、年龄、性别均无统计学差异的患者,出院后查阅其病历资料,记录慢性并发症：糖尿病眼病、糖尿病肾病、糖尿病大血管病变（颈部及双下肢血管）、糖尿病周围神经病变、糖尿病植物神经病变。采用χ2检验分析得分≥60分及〈60分者慢性并发症发病率差异。结果14例糖尿病患者相关知识掌握好（得分≥85分）,占9.3%,45例一般（60~84分）,占30%,91例差（〈60分）占60.7%;糖尿病教育相关知识得分〈60分组患者其慢性并发症的发病率均明显高于得分≥60分组（P〈0.05）。结论糖尿病健康教育知识掌握好坏直接影响糖尿病慢性并发症的发生率,本市农村糖尿病健康教育形势严峻,需引起有关部门及广大医务工作者的重视。     

糖尿病下肢血管病变药物治疗综述

糖尿病下肢血管病变为糖尿病常见的慢性并发症之一。及早给予药物治疗不仅能有效缓解症状,还能积极预防血管并发症的发生,延缓疾病的发展,降低截肢率,对糖尿病下肢血管病变的预后具有重要意义。本文综述糖尿病下肢血管病变的药物治疗现状。     

2型糖尿病下肢血管病变相关因素分析及干预

目的:探讨影响2型糖尿病合并下肢血管病变的危险因素.方法:对40例2型糖尿病患者根据有无下肢血管病变进行分组分析.比较空腹血糖、餐后2小时血糖、糖化血红蛋白、血脂、年龄、病程、高血压及相关并发症等.结果:糖尿病有下肢血管病变组的年龄较无病变组明显升高(P<0.01)、病程明显延长(P<0.01)、糖化血红蛋白水平明显升高(P<0.01);血脂异常及收缩压(SBP)明显升高(P<0.05);而两组间的FBG、PBG、舒张压(DBP)无显著差异性(P>0.05).结论:糖尿病下肢血管病变的发生可能与年龄、病程、糖化血红蛋白、血脂水平、血压等多种危险因素综合作用有关.     

血管紧张肽转换酶抑制药和糖尿病

血管紧张肽转换酶抑制药可增加组织对内源性和外源性胰岛素的敏感性。血管紧张肽转换酶抑制药通过扩张肾小球入球小动脉和出球小动脉、降低肾小球囊内压力 ,可延迟糖尿病肾病的发生。血管紧张肽转换酶抑制药通过降低血压、减少血管紧张肽Ⅱ的不利作用、抗血管平滑肌增殖作用、抗心力衰竭作用可减少糖尿病心血管并发症的发生。血管紧张肽转换酶抑制药尚有利于糖尿病眼部并发症、周围神经病变的治疗     

妊娠期糖尿病184例临床分析

目的探讨妊娠期糖尿病治疗效果对妊娠结局的影响。方法2005年1月-2008年8月我院检查确诊为妊娠期糖尿病（GDM）并在院分娩的孕妇共184人,按治疗效果分为血糖控制理想组（Ⅰ组）和血糖控制不理想组（Ⅱ组）,比较两组的妊娠结局及分娩情况。结果两组的剖宫产率、妊娠期高血压疾病、胎儿生长受限、羊水过多、产后出血、胎儿宫内窘迫的发生率经统计学处理有显著性差异（P〈0.05）,两组早产、产褥感染、巨大胎儿、新生儿窒息及新生儿低血糖的发生率有显著性差异（P〈0.01）,两种分娩方式对比产后出血、产褥感染、胎儿宫内窘迫、新生儿窒息、新生儿低血糖发生率无统计学差异。结论妊娠期糖尿病孕妇经过合理规范治疗使血糖水平得到有效控制,其妊娠结局能得到明显改善,应加强对GDM的管理。     

精神分裂症合并糖尿病患者临床特征的对照研究

目的探讨精神分裂症合并糖尿病患者的临床特征。方法使用自制调查表，收集30例精神分裂症合并糖尿病患者和30例单纯精神分裂症患者。结果精神分裂症合并糖尿病的患者，平均病程，复发次数和平均住院日显著高于单纯精神分裂症患者（P〈0．05或〈0．01）。精神分裂症合并糖尿病患者的临床症状显著重于单纯精神分裂症患者（P〈0．05或〈0．01）。精神分裂症合并糖尿病患者的疗效显著低于单纯精神分裂症患者（P〈0．01）。结论精神分裂症合并糖尿病患者的临床症状重，治疗难度大。     

白藜芦醇对2型糖尿病患者外周血单个核细胞DNA损伤的体外修复

目的:观察2型糖尿病(T2DM)患者氧化/抗氧化状态、外周血单个核细胞(PBMCs)DNA损伤情况及白藜芦醇的体外修复作用。方法:采用单细胞凝胶电泳技术检测39例T2DM血管并发症、29例T2DM无并发症患者PBMCsDNA损伤情况(用彗星率表示),并与26名体检健康者对照比较。检测受试者血浆总抗氧化能力(TAC)、丙二醛(MDA)及巯基(SH)含量。观察白藜芦醇在体外对T2DM患者PBMCsDNA损伤的修复作用。结果:T2DM无并发症组PBMCs彗星率及血浆MDA含量明显高于健康对照组(P<0.01),血浆SH含量、TAC明显低于健康对照组(P<0.01);T2DM血管并发症组彗星率及MDA含量高于无并发症组(或P<0.05),TAC低于无并发症组(P<0.05)。T2DM无并发症组及血管并发症组患者彗星率与MDA含量呈正相关(r分别为0.446、0.504,P<0.05),与TAC呈负相关(r分别为-0.418、-0.399;P<0.05)。体外修复显示:10μmol·L-1白藜芦醇作用4h显著降低了T2DM患者PBMCs彗星率(P<0.01)。结论:T2DM患者体内存在氧化/抗氧化失衡、DNA氧化损伤,血管并发症组重于无并发症组。氧化应激可能参与了T2DM患者血管并发症的发生发展。抗氧化剂白藜芦醇在体外减轻T2DM患者PBMCsDNA损伤。     

不同剂量阿托伐他汀对2型糖尿病患者心血管并发症的影响

目的:观察不同剂量阿托伐他汀对2型糖尿病患者心血管并发症的影响.方法:将150例2型糖尿病患者随机分为3组,对照组50例、常规降脂组50例(阿托伐他汀20 mg/d)、强化降脂组50例(阿托伐他汀40 mg/d).各组常规治疗包括抗血小板治疗和降糖(药物和/或胰岛素)治疗.均随访3年,观察各治疗组心血管并发症的发生情况,评价治疗效果.结果:与对照组相比,常规降脂组和强化降脂治疗后组TC、低密度脂蛋白-胆固醇(LDL-C)显著下降(P＜0.01),高密度脂蛋白-胆固醇(HDL-C)显著升高(P＜0.01).常规降脂组与强化降脂组治疗后比较,TC、LDL-C下降程度和HDL-C升高程度比较差异有统计学意义(P＜0.01).3年内主要心血管并发症与对照组相比,强化降脂组与常规降脂组比例明显降低(P＜0.05),且强化降脂组较常规降脂组心血管并发症发生比例明显降低(P＜0.05).结论:阿托伐他汀能显著减少2型糖尿病患者心血管并发症的发生,且强化降脂治疗效果更佳,无明显不良反应.     

eNOS:糖尿病内皮祖细胞功能失调的一个关键因素

糖尿病是由多种病因引起的,以慢性高血糖为特征的代谢紊乱综合征。糖尿病患者内皮祖细胞(EPCs)数目减少,动员、迁移、归巢、分化能力明显降低,这可能是引起糖尿病大血管并发症的主要原因之一。内皮型NO合酶(eNOS)是调节内皮祖细胞功能的关键酶。该文就eNOS与糖尿病内皮祖细胞功能失调的相关性进行综述,为糖尿病治疗提供新的思路。     

镇痛灵对糖尿病并发症的防治作用

目的：研究镇痛灵（SP）对Wistar糖尿病大鼠生殖功能的影响机制。方法：3～5月龄舍Wistar鼠75只，随机分为糖尿病组60只，尾静脉注射1．5％四氧嘧啶50mg·kg；正常对照组15只，尾静脉注射等体积生理盐水。72h后，以血糖值大于16．67mol·L^-1为造模成功。将糖尿病大鼠随机分为4组，模型组和3种不同剂量镇痛灵治疗组。第5周乙醚麻醉下断头取血，分离血清测生化指标。取一侧睾丸组织，制备病理切片，光镜观察；另一侧制成匀浆液，待测组织成份。结果：（1）糖尿病大鼠与正常对照组比较，血清一氧化氮、一氧化氮合酶、血清总抗氧化能力明显降低，差异有极显著性（P〈0．01）；黄嘌呤氧化酶值升高（P〈0．01）；（2）中、高剂量治疗组血清一氧化碳、一氧化碳合酶、血清总抗氧化能力值与模型组比较明显升高，差异有显著性（P〈0．05）；黄嘌呤氧化酶值降低（P〈0．05）。低剂量治疗组各指标变化与模型组比较，差异无显著性（P〉0．05）；（3）糖尿病大鼠睾丸病理改变明显，经中、高剂量镇痛灵治疗后，损害的间质细胞、生精细胞数量和形态恢复正常。结论：镇痛灵对糖尿病并发的生殖功能障碍有防治作用，并在一定剂量范围内呈量效依赖关系。     

Potential roles of ellagic acid on metabolic variables in diabetes mellitus: A systematic review

Diabetes mellitus is a widespread endocrine disorder globally. Due to its antioxidant and anti-inflammatory properties, ellagic acid has the potential to improve the metabolic effects of chronic non-communicable diseases. This systematic review summarizes current evidence about the potential effects of ellagic acid on metabolic variables in diabetes mellitus. A comprehensive systematic literature search was conducted in databases such as PubMed, Scopus, EMBASE, ProQuest and Google Scholar from inception until March 2022. All animal studies and clinical trials were eligible for inclusion. Studies using in vitro models or published in a non-English language were excluded. Of 1320 articles, 23 were selected for assessment, including 21 animal studies and two randomized controlled trial studies. Following ellagic acid administration, findings reported improvement in FBS, HbA1c, insulin (20, 8 and 12 studies, respectively), TG, TC, HDL-C (13, 10 and 5 studies, respectively), MDA, GSH, CAT, SOD (11, 6, 3 and 4 studies, respectively), and TNF-α and IL-6 (6 and 3 studies, respectively). In conclusion, ellagic acid may improve glycaemic indicators, dyslipidaemia, oxidative stress and inflammation in diabetes mellitus. However, further clinical trials are needed to explore the mechanisms more precisely and to observe the applied consequences.