维药罗补甫克比日丸对DM性勃起功能障碍大鼠性激素水平的影响

目的:揭示维药罗补甫克比日丸对糖尿病(DM)性勃起功能障碍(ED)大鼠性激素水平的影响。方法:取50只SD雄性大鼠,从中随机取7只设为正常对照(A)组,余43只行腹腔注射链尿佐菌素(STZ)制造DM动物模型,未成模者为STZ组,成模者用阿朴吗啡(APO)筛选DM性ED模型,并将其随机分为DM性ED对照组、药罗补甫克比日丸(C)组、胰岛素(D)组、联用(E)组,未成ED模者为DM(F)组,共7组。药物干预6周后,检测外周血中性激素水平。结果:正常对照(A)组、DM性ED胰岛素(D)组、DM性ED联用(E)组、STZ(G)组睾酮(T)水平显著高于DM性ED对照(B)组、DM性ED伊木萨克(C)组、DM(F)组,有显著性差异(P0.01);正常对照(A)组、STZ(G)组促黄体生成激素(LH)水平显著低于DM性ED伊木萨克(C)组、DM性ED联用(E)组,有显著性差异(P0.05、P0.01);DM性ED对照(B)组、DM性ED补甫克比日丸(C)组促卵泡刺激素(FSH)水平显著低于DM性ED胰岛素(D)组、DM性ED联用(E)组,有显著性差异(P0.01、P0.05)。结论:维药罗补甫克比日丸可显著改善DM性ED大鼠睾酮水平,且与胰岛素联用优于单用,维药罗补甫克比日丸治疗DM性ED的作用机制可能与T、LH、FSH含量变化有关。     

糖尿病基因治疗的新进展

目前,糖尿病的基因治疗主要分为替代基因治疗、免疫基因治疗和调节基因治疗三部分.近年来,随着人们对糖尿病本质的深层次揭示和现代分子生物学手段的发展,糖尿病基因治疗的内容不断增加.如：对K细胞的新认识,发现了胰腺十二指肠同源异形盒基因1(PDX-1)的新价值及单链胰岛素类似物基因的构建成功等.另外,还利用各种方法来提高转染效率,增加安全性.如使用腺病毒(HD)载体,应用电穿孔法(electroporation)等.     

基因治疗糖尿病的研究进展

随着基因转移技术的进步,引导了在分子水平研究替代正常胰岛素释放功能的方法,葡萄糖刺激胰岛素分泌的β细胞系和非β细胞系的构建已有一定的进步,胰岛素基因直接转染给动物体内可以控制血糖.因此,细胞工程和基因疗法必将会为糖尿病治疗开拓广阔的前景.     

2 型糖尿病治疗药物研究进展

2 型糖尿病（T2DM）是一种代谢障碍性疾病。传统抗糖尿病药物具有不同程度的副作用,如低血糖、胃肠道反应、体重增加、 心血管风险等,因此开发作用于新靶点和新作用机制的T2DM 治疗新药成为当前研究的热点。目前基于新靶点设计的糖尿病治疗新药有 些已上市,且获得良好的降糖效果,但大部分药物仍处于临床或临床前研究阶段,其疗效和安全性有待进一步临床验证。综述传统抗糖 尿病药物、T2DM 药物新靶点及基于新靶点设计的抗糖尿病新药的研究进展。     

Endothelial Dysfunction in Obesity and Insulin Resistance: A Road to Diabetes and Heart Disease

Obesity, insulin resistance, and endothelial dysfunction closely coexist throughout the natural history of type 2 diabetes. They all can be identified not only in people with type 2 diabetes, but also in various groups at risk for the disease, such as individuals with impaired glucose tolerance, family history of type 2 diabetes, hypertension, dyslipidemia, prior gestational diabetes, or polycystic ovary syndrome. Whereas their evident association cannot fully establish a cause‐effect relationship, fascinating mechanisms that bring them closer together than ever before are rapidly emerging. Central or abdominal obesity leads to insulin resistance and endothelial dysfunction through fat‐derived metabolic products, hormones, and cytokines. Insulin resistance leads to endothelial dysfunction through the frequent association with traditional cardiovascular risk factors and through some more direct novel mechanisms. Some specific and shared insulin signaling abnormalities in muscle, fat, and endothelial cells, as well as some new genetic and nontraditional factors, may contribute to this interesting association. Some recent clinical studies demonstrate that nonpharmacological and pharmacological strategies targeting obesity and/or insulin resistance ameliorate endothelial function and low‐grade inflammation. All these findings have added a new dimension to the association of obesity, insulin resistance, and endothelial dysfunction that may become a key target in the prevention of type 2 diabetes and cardiovascular disease.     

血府逐瘀丸治疗老年2型糖尿病伴失眠的临床疗效及其对认知功能的影响

目的:探究血府逐瘀丸治疗老年2型糖尿病伴失眠患者的临床疗效及其对认知功能影响。方法:选取43例我院收治的老年2型糖尿病伴失眠患者,将其随机分为实验组及对照组。对照组21例予地西泮治疗,实验组22予血府逐瘀丸治疗。观察两组治疗前后失眠症状及认知功能的变化情况。结果:治疗后,实验组总有效率(86.4%)高于对照组(61.9%),其差异经比较有统计学意义(P0.05);两组匹兹堡睡眠质量指数量表(PSQI)评分均较治疗前显著降低(P0.05),与对照组相比,实验组PSQI评分较低(P0.05),空腹血糖水平较低(P0.05),蒙特利尔认知评估量表(MoCA)评分较高(P0.05)。结论:血府逐瘀丸可有效降低老年2型糖尿病伴失眠患者的血糖水平,提升睡眠质量,改善失眠及认知功能障碍。     

A Role for the Endothelial Glycocalyx in Regulating Microvascular Permeability in Diabetes Mellitus

Diabetic angiopathy is a major cause of morbidity and mortality in diabetes mellitus. Endothelial dysfunction and associated alterations in blood flow, pressure and permeability are widely accepted phenomena in the diabetic milieu and are understood to lead to microangiopathy. Despite the clinical importance of diabetic microangiopathy, the mechanisms of pathogenesis remain elusive. In particular, much is yet to be understood about the nature of the putative increased permeability with respect to diabetes. Microvessel permeability is intrinsically difficult to measure and a surrogate (solute or solvent flux) is usually reported, the measurement of which is hampered by haemodynamic factors, such as flow rate, hydrostatic pressure gradient, solute concentration and surface area available for exchange. Very few studies describing the measurement of permeability with respect to diabetes have controlled for all these factors. As a result, the nature of the increased microvessel permeability in diabetes mellitus and indeed its causes are poorly understood. Recent studies have shown that hyperglycaemia can alter the glycocalyx structure, and parallel findings have shown that the apparent increase in permeability demonstrated in hyperglycaemia may be due to an increase in the permeability of the vessels to water, and not an increase in protein permeability, an effect attributable to altered glycocalyx. This review focuses on the current understanding of microvascular permeability in terms of the endothelial glycocalyx- fibre-matrix theory, those methods used to determine permeability in the context of diabetes, and the more recent developments in our understanding of elevated microvascular permeability in the diabetic circulation.     

2型糖尿病合并下肢动脉粥样硬化的危险因素

下肢动脉粥样硬化是2型糖尿病(T2DM)患者最常见的大血管并发症之一。作为T2DM患者严重的慢并发症之一,下肢动脉粥样硬化可引起糖尿病足的发生,严重情况下可导致足坏疽。因此,阐明T2DM合并下肢动脉粥样硬化的危险因素,早期预防和治疗糖尿病合并下肢动脉粥样硬化症,不仅提高了患者的生活质量,而且减轻了家庭和社会的经济负担,具有较大的现实意义。影响T2DM患者下肢动脉粥样硬化的因素错综复杂,分为不可调控的和可调控的因素,不可调控的危险因素包括年龄、种族、遗传等,可调控的危险因素包括吸烟、高血糖、高血脂、高血压,以及近年提出的肥胖、胰岛素抵抗、高纤维蛋白血症、炎症等。本文就T2DM合并下肢动脉粥样硬化的危险因素做一综述。     

中药治疗糖尿病的研究概况

从单味中药及有效成分、有效部位,中药复方,作用机制等方面对近年来中药治疗糖尿病的研究概况进行综述,为进一步从中药中研制治疗糖尿病的创新药物提供参考。     

小檗碱抗氧化和抗炎作用用于糖尿病治疗的机制研究进展

研究表明氧化应激反应和慢性炎症反应是2型糖尿病糖、脂代谢紊乱和胰岛素抵抗发生的重要病理机制。小檗碱是中药黄连的主要有效成分之一。体内、外研究证实小檗碱可通过抗氧化和抗炎作用发挥对2型糖尿病的治疗作用。本文就小檗碱抗氧化和抗炎作用用于2型糖尿病治疗的分子机制研究进展作一综述。小檗碱抗氧化和抗炎作用机制复杂,目前的研究显示小檗碱可通过AMPK通路、MAPK通路、Nrf2通路和NF-κB通路发挥抗氧化和抗炎作用。然而,小檗碱的抗氧化和抗炎作用仍需进一步的深入研究证实。明确小檗碱的抗氧化和抗炎作用的分子机制,有助于进一步了解小檗碱治疗糖尿病作用的机理,为探寻治疗糖尿病的天然药物提供理论依据。     

妊娠糖尿病饮食相关危险因素分析

目的：通过分析妊娠糖尿病患者与正常孕妇的饮食行为,探讨妊娠糖尿病发病饮食相关的危险因素,为孕期妇女提供科学 合理膳食指导。方法：采用多阶段连续等比例抽样,选取确诊GDM的孕妇150 例为病例组,同期就诊非GDM孕妇150 例为对照 组,利用24 小时膳食回顾法进行饮食行为和一般情况的问卷调查。采用Logistic 回归筛选GDM 饮食相关危险因素。结果：多因 素Logistic 回归分析显示,怀孕年龄( OR=1.157)、孕前BMI(OR=1.780)、糖尿病家族史(OR=2.448)、产次(OR=1.157)、总能量、水果 摄入量(OR=4.109)、豆类（OR=0.998）与妊娠糖尿病发生相关（OR=0.998）。采用多变量模型具体分析水果的摄入量,同时调整与妊 娠糖尿病发生的相关因素结果显示：与水果摄入量小于200 g/d 相比,水果的摄入量200 ~ 400 g/d,400 ~ 600 g/d 和超过600 g/d 其OR值分别为0.38、2.48、2.63（P<0.01）。结论：除高龄、肥胖、糖尿病家族史等妊娠糖尿病高危因素外,饮食行为与GDM存在一 定的相关性。针对高危人群早期干预,同时对孕期妇女进行科学合理的饮食指导,调整饮食结构,控制食物摄入量,以减少GDM 的发病。     

家族高发性2型糖尿病的遗传模式研究

对1999～2000年门诊及住院的家族高发性2型糖尿病患者为先证者的136个大家系进行研究,以探讨该病的遗传模式。对家系人群采用Falconer 法估算遗传率,用Penrose法进行多基因分析,并用S.A.G.E-REGD软件拟合A型回归Logistic模型进行复合分离分析的方法,对家族高发性2型糖尿病家系进行研究。结果表明,136个大家系的2型糖尿病遗传率为94.07%±5.84%,提示在这些家系中可能有显性主基因存在。多基因分析研究表明,在该人群中,2型糖尿病因性别不同而存在两种遗传模式。复合分离分析拒绝单纯环境模型、非传递模型、共显性模型,接受隐性模型和显性模型,但隐性模型为最佳遗传模式。因此,2型糖尿病具有高度的遗传性和遗传异质性,总体表现为多因子遗传,在部分遗传背景较一致的家系人群中可能存在由主要基因决定的常染色体显性遗传。 Abstract:This study is to explore the genetic model of type 2 diabetes mellitus (type 2 DM) among the hereditary family.One hundred and thirty-six pedigrees of familial type 2 DM were studied.The heritability of type 2 DM was estimated according to Falconer's method and the multi-factorial inheritance analyzed according to Penrose's method.Complex segregation analysis was performed using S.A.G.E-REGD.The heritability of familial type 2 DM was 9407%±5.84%.Dominant major gene might influence the genesis of type 2 DM.Analysis of multi-factorial inheritance indicated that there be two genetic patterns respectively in male and female populations.By complex segregation analysis,environment,non-transmitted and co-dominant inheritance were rejected.Autosomal dominant (AD) inheritance and autosomal recessive (AR) inheritance was accepted but AR inheritance was the best pattern.This study suggested that type 2 DM had significant heritability and genetic heterogeneity,which appeared to be a disease of multi-factorial inheritance generally and autosomal dominant (AD) inheritance in part of pedigrees.     

脂肪因子在糖尿病认知功能障碍中的调控作用及运动干预机制

糖尿病认知功能障碍指糖尿病患者伴有认知功能损伤，是一种常见的糖尿病并发症，尤其高发于老年2型糖尿病患者。研究表明，脂肪组织分泌的细胞因子，如脂联素（adiponectin,APN）和瘦素（leptin,LEP）等不仅能够调节能量代谢，还与糖尿病认知功能障碍的发生发展密切相关，可能作为糖尿病相关认知功能障碍的生物标志物。APN和LEP能够穿过血脑屏障进入大脑，通过结合神经元或神经胶质细胞（如小胶质细胞和星形胶质细胞）上的受体，激活或抑制胞内下游的p38 MAPK、AMPK、ERK、JAK2/STAT3、PI3K/AKT和SIRT1/PGC-1α等信号通路，调节海马神经发生、突触可塑性、神经炎症、氧化应激和神经元凋亡等生理进程，进而调控认知功能。重要的是，APN和LEP还可能作为运动改善糖尿病认知功能障碍的重要介质。通过剖析APN和LEP与糖尿病认知功能障碍之间的关系，梳理APN和LEP调控认知功能的潜在生物学机制，探讨运动介导APN和LEP改善糖尿病认知功能障碍的可能机制，旨在为进一步丰富“脂-脑”crosstalk理论体系，制定并完善糖尿病认知功能障碍的诊疗策略开拓思路。     

胰岛素对不同孕期妊娠糖尿病患者血糖水平及妊娠结局的影响

目的:探讨胰岛素对不同孕期妊娠合并糖尿病孕产妇血糖水平及妊娠结局的影响。方法:选择2011年7月-2015年4月在我院接受治疗的妊娠期糖尿病患者200例,均采用胰岛素治疗。检测患者血糖变化、妊娠期并发症的发生情况,并分析孕期对胰岛素治疗效果的影响。结果:治疗后产妇空腹血糖及餐后2 h血糖均低于治疗前,差异具有统计学意义(P0.05);孕期32周的产妇治疗后空腹血糖及餐后2 h血糖均低于孕期≥32周的产妇,差异具有统计学意义(P0.05)。孕期32周的产妇妊娠高血压及产后出血的发生率均低于孕期≥32周的产妇,但早产及剖宫产的发生率高于孕期≥32周的产妇,差异具有统计学意义(P0.05)。结论:胰岛素治疗能够有效控制妊娠期糖尿病产妇的血糖水平,改善妊娠结局,早期干预效果较好。     

骨髓间充质干细胞分化为胰岛细胞治疗糖尿病

糖尿病已成为严重危害人类健康的疾病之一。目前,移植胰岛治疗糖尿病已初见疗效,但由于胰岛来源匮乏和免疫排斥反应而受阻。骨髓间充质干细胞(bonemarrowmesenchymalstemcells,BMMSCs)取材方便,容易进行体外分离、培养和纯化,且具有跨越分化潜能。若将自体BMMSCs诱导分化为胰岛细胞,可望解决细胞来源和免疫排除问题,实现糖尿病的自体细胞治疗。现对体外诱导BMMSCs分化为胰岛细胞治疗糖尿病的研究进展进行综述,并指出了存在问题和今后的研究方向。     

Hippocampal Neuropathology of Diabetes Mellitus is Relieved by Estrogen Treatment

1. A recently recognized complication of uncontrolled diabetes mellitus is the encephalopathy involving, among other regions, the hippocampus. Since estrogens bring neuroprotection in cases of brain injury and degenerative diseases, we have studied if estradiol (E2) administration counteracts some hippocampal abnormalities of streptozotocin (STZ)-diabetic adult mice.2. We first report the ability of E2 to modulate neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ) of diabetic mice. Using bromodeoxyuridine (BrdU) to label newly generated cells, a strong reduction in cell proliferation was obtained in DG and SVZ of mice sacrificed 20 days after STZ administration. The reduction was completely relieved by 10 days of E2 pellet implantation, which increased 30-fold the circulating E2 levels.3. Diabetic mice also showed abnormal expression of astrocyte markers in hippocampus. Thus, increased number of GFAP⁺ cells, indicative of astrogliosis, and increased number of apolipoprotein-E (Apo-E)⁺ astrocytes, a marker of ongoing neuronal dysfunction, was found in stratum radiatum below the CA1 hippocampal subfield of diabetic mice. Both parameters were reverted to normal by the E2 regime that upregulated cell proliferation.4. The studies demonstrated that hippocampal neuropathology of uncontrolled diabetes is a reversible condition and sensitive to estrogen treatment. Studies in animal models may open up new venues for understanding the beneficial role of steroid hormones in diabetic encephalopathy.     

妊娠期糖尿病小鼠胎盘EGFR的表达与其发病关系的研究

目的:研究妊娠期糖尿病小鼠胎盘表皮生长因子受体(EGFR)的表达,探讨EGFR表达与妊娠期糖尿病发病的关系。方法:采用链脲佐菌素建立妊娠期糖尿病(gestational diabetes mellitus,GDM)小鼠模型,对照组为正常妊娠小鼠,腹腔注射等量缓冲溶液。测定母鼠体重、血糖;计算胎鼠的存活率;测定胎鼠、胎盘重量,计算胎盘效率;RT-PCR、免疫组化分别测定GDM组和对照组胎盘EGFR m RNA和EGFR蛋白的表达。Pearson相关性分析用于母鼠血糖与EGFR表达的相关性分析。结果:GDM组母鼠体重和血糖均高于对照组(P0.01);GDM组胎鼠、胎盘重量及胎盘效率均高于对照组(P0.01);RT-PCR和免疫组化结果显示GDM组胎盘EGFR m RNA和EGFR蛋白的表达与对照组相比差异有统计学意义(P0.01)。GDM组小鼠血糖值与其胎盘EGFR的表达具有相关性(r=0.582,P0.05)。结论:GDM导致胎盘EGFR表达升高,EGFR并不是GDM的发病因素,EGFR是预防GDM的潜在靶点。     

厄贝沙坦联合氨氯地平治疗2 型糖尿病合并高血压的疗效及对糖代谢和 血压的影响

目的：探索厄贝沙坦联合氨氯地平治疗2型糖尿病合并高血压的疗效及对糖代谢和血压的影响。方法：选择2013年7 月至 2014 年8月期间我院收治的2 型糖尿病合并高血压患者50 例,根据随机数字表法,将患者分成联合用药组和美托洛尔组。联合 用药组口服厄贝沙坦和氨氯地平;美托洛尔组口服美托洛尔,疗程为3个月。分析比较治疗前后两组患者的空腹血糖（FBG）、空腹 胰岛素（FINS）、胰岛素敏感指数（HOMA-IR）、收缩压（SBP）和舒张压（DBP）水平之间的差异,观察临床疗效。结果：治疗后,两组 患者FBG、FINS、HOMA-IR、SBP和DBP 水平较治疗前均有所下降,其中联合用药组下降得更明显（P<0.05）,且治疗后联合用药 组上述指标均显著低于美托洛尔组,差异均有统计学意义（P<0.05）。治疗后,联合用药组的治疗有效率为88.00%,显著高于美托 洛尔组的48.00%,且差异具有统计学意义（P<0.05）。结论：厄贝沙坦联合氨氯地平治疗2 型糖尿病合并高血压患者具有良好的疗 效,可以改善血糖和血压情况,对于指导临床用药具有重要意义。     

硫化氢在糖尿病及其并发症中作用的研究进展

糖尿病及其并发症是覆盖全球的常见疾病,发病率逐年增高。硫化氢是继一氧化氮和一氧化碳之后的第三种气体信号分子,发挥重要病理生理学效应。目前研究发现,硫化氢在调节胰岛β细胞功能、胰岛素抵抗和糖尿病并发症中发挥着重要作用,已经成为糖尿病及其并发症的研究热点。本篇综述就H_2S在糖尿病及其并发症中发挥的病理生理学作用及机制进行了阐述。