几种实验性2型糖尿病动物模型制备方法的比较

2型糖尿病是一种严重影响人类健康的内分泌代谢性疾病,其患病人数多,病程缓慢。动物模型在2型糖尿病研究中发挥了重要作用,其中实验性动物模型因其价格便宜,易于诱导和维持而被广泛应用。本文对几种常见的2型糖尿病动物模型的建立方法进行综述和评价。     

几种实验性2型糖尿病动物模型制备方法的比较

2型糖尿病是一种严重影响人类健康的内分泌代谢性疾病,其患病人数多,病程缓慢。动物模型在2型糖尿病研究中发挥了重要作用,其中实验性动物模型因其价格便宜,易于诱导和维持而被广泛应用。本文对几种常见的2型糖尿病动物模型的建立方法进行综述和评价。     

小型猪模型在人类内分泌代谢性疾病研究中的应用进展

内分泌代谢性疾病(metabolic and endocrine diseases)是危害人类健康、降低生活质量的重要病症之一。肥胖、病毒感染、遗传易感性及免疫功能异常等多种因素均可导致内分泌代谢性疾病的发生,但其致病机制仍不明确。制备适宜动物模型是开展相关研究的关键基础。小型猪在生理解剖结构、机体代谢过程、病理诊断指标等方面与人类极为相似,是制备内分泌代谢性疾病的理想动物模型。本文对小型猪品系、构建疾病模型的方法及现状展开综述,旨在为人类内分泌代谢性疾病动物模型相关研究提供参考。     

类风湿性关节炎啮齿动物模型的研究进展

类风湿性关节炎是一种常见的致残性疾病之一,病因未明。研究此类疾病的有效方法是建立、研究并应用动物模型。通过对目前国内外类风湿性关节炎模型复制方法、机制和应用的研究,分析各自的特点及不足之处,提出复制更加符合类风湿性关节炎临床特点的动物模型的展望与设想。     

代谢病相关的遗传工程小鼠模型

糖尿病及肥胖症等代谢性疾病已成为影响人类健康的主要疾病,属于多基因所致的代谢综合征,遗传模式复杂多样,至今仍所知甚少。理想的实验动物模型是我们深入了解代谢病病因、遗传及环境因素的必要工具,并且可以用来研究验证新的治疗药物。近年来,已经获得了大量的遗传工程动物模型,包括转基因、基因敲除模型等遗传工程动物,对于代谢性疾病的研究意义重大。本文主要介绍近年来应用较多的糖尿病及肥胖相关的遗传工程小鼠模型遗传特征及应用。     

阿尔茨海默病动物模型研究进展

阿尔茨海默病(Alzheimer's disease,AD)是一种以认知功能障碍为主要特征,随着年龄增长症状逐渐加重的神经退行性疾病.由于世界人口结构老龄化愈来愈严重,对AD疾病的研究也成为世界医学界的热点.对疾病机制的研究需要建立与临床病理特征相符的动物模型.关于AD动物模型的建立方法有仿人类衰老过程的自然衰老动物模...     

卵巢早衰动物模型制备研究进展

卵巢早衰是一种典型异质性疾病,病因复杂多样。近年来,卵巢早衰的发病率有明显上升趋势,严重影响妇女身心健康和生活质量。建立一种理想可靠的卵巢早衰动物模型对研究卵巢早衰有着重要的临床意义。本文就国内外学者建立的卵巢早衰动物模型作一综述,讨论比较各种方法的优缺点。     

我国疾病动物模型的研究现状和展望

由于医学科学研究的需要,各类疾病动物模型被广泛用来研究人类疾病的发生发展机制、药物筛选以及治疗评价等.本文全面梳理了我国疾病动物模型的研究和发展现状,分析了我国在这方面的特色优势以及与国际上的差距,内容涵盖了肿瘤、神经及精神疾病、感染及免疫性疾病、心血管与代谢性疾病、药物筛选等不同领域.简要介绍了国家自然科学基金对疾病动物模型项目的资助情况,同时指出了我国疾病模型今后的主要发展方向.     

瘦素受体基因敲除SD大鼠的表型及病理观察

目的观察CRISPR/Cas9技术建立的肥胖、代谢综合征和糖尿病前期特征的瘦素受体基因敲除大鼠模型的多种参数,为代谢性疾病的分子机制研究和新药研发提供更为理想的动物模型。方法1)定期测定Lepr^-/-大鼠的体重、摄食量、随机血糖和空腹血糖;葡萄糖耐量试验和胰岛素耐量试验;血清血脂参数;2)观察14周和18周Lepr^-/-大鼠主要脏器的病理学改变;3)观察脏器脂质沉积情况。结果Lepr^-/-大鼠表现明显肥胖、高摄食量、葡萄糖耐量受损、胰岛素抵抗和血脂异常;14周和18周出现胰岛增生和心脏肌细胞肥大、脂肪肝、肥胖相关性肾病;肝细胞、肾小管上皮细胞和骨骼肌纤维内脂质沉积。结论Lepr^-/-大鼠是代谢性疾病的病因研究和新药研发的理想动物模型。     

成年生长激素缺乏动物模型与骨代谢相关研究进展

目的探讨成年生长激素缺乏动物模型的几种建立方法,为实验研究和治疗因生长激素缺乏引起的骨代谢异常提供良好的模型。方法通过查阅文献,对成年生长激素缺乏动物模型的建立方法进行综述和评价。结果成年生长激素缺乏动物模型可分为自发性生长激素缺乏动物模型、垂体切除动物模型、基因敲除模型三种。结论垂体切除动物模型价格低廉,可操作性强,但受影响的因素较多,不适合于生长激素与骨代谢之间关系的研究;自发性生长激素缺乏动物模型与基因敲除动物模型价格高昂,但特异性缺乏生长激素,利于研究生长激素缺乏对骨代谢的影响。     

Focus: Microbiome: Treating Obesity and Metabolic Syndrome with Fecal Microbiota Transplantation

The worldwide prevalence of metabolic syndrome, which includes obesity and its associated diseases, is rising rapidly. The human gut microbiome is recognized as an independent environmental modulator of host metabolic health and disease. Research in animal models has demonstrated that the gut microbiome has the functional capacity to induce or relieve metabolic syndrome. One way to modify the human gut microbiome is by transplanting fecal matter, which contains an abundance of live microorganisms, from a healthy individual to a diseased one in the hopes of alleviating illness. Here we review recent evidence suggesting efficacy of fecal microbiota transplant (FMT) in animal models and humans for the treatment of obesity and its associated metabolic disorders.     

Disrupted chronobiology of sleep and cytoprotection in obesity: possible therapeutic value of melatonin

From a physiological perspective the sleep-wake cycle can be envisioned as a sequence of three physiological states (wakefulness, non-rapid eye movement, NREM, sleep and REM sleep) which are defined by a particular neuroendocrine-immune profile regulating the metabolic balance, body weight and inflammatory responses. Sleep deprivation and circadian disruption in contemporary "24/7 Society" lead to the predominance of pro-orexic and proinflammatory mechanisms that contribute to a pandemic metabolic syndrome (MS) including obesity, diabetes and atherosclerotic disease. Thus, a successful management of MS may require a drug that besides antagonizing the trigger factors of MS could also correct a disturbed sleep-wake rhythm. This review deals with the analysis of the therapeutic validity of melatonin in MS. Melatonin is an effective chronobiotic agent changing the phase and amplitude of the sleep/wake rhythm and having cytoprotective and immunomodulatory properties useful to prevent a number of MS sequels. Several studies support that melatonin can prevent hyperadiposity in animal models of obesity. Melatonin at a low dose (2-5 mg/day) has been used for improving sleep in patients with insomnia and circadian rhythm sleep disorders. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects (ramelteon, agomelatine, tasimelteon, TK 301). In clinical trials these analogs were employed in doses considerably higher than those usually employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin doses in the range of 50-100 mg/day are needed to assess its therapeutic value in MS.     

非酒精性脂肪肝与脂肪性肝炎动物模型研究进展

非酒精性脂肪肝是无酒精滥用的包括单纯性脂肪肝、脂肪性肝炎、脂肪性肝纤维化和肝硬化的肝病综合征,目前已成为广受关注的肝病医学难题。随着抗脂肪肝药物的深入研究,动物模型制作得到很好发展。近年来,在大鼠、沙鼠、小鼠、兔和小猪等动物种属成功地建立了食物、胃肠外营养与蛋氨酸胆碱缺乏等诱导的单纯性脂肪肝和脂肪性肝炎动物模型,这些模型为研究脂肪肝和脂肪性肝炎的发病机理与治疗提供了机会。每种动物模型各有优缺点,合理应用动物模型能更好地开展脂肪肝病的实验和临床研究。本文综述了非酒精性脂肪肝及脂肪性肝炎动物模型制作方法的若干研究进展。     

Heightened efficacy of nitric oxide-based therapies in type II diabetes mellitus and metabolic syndrome

Type II diabetes mellitus (DM) and metabolic syndrome are associated with accelerated restenosis following vascular interventions due to neointimal hyperplasia. The efficacy of nitric oxide (NO)-based therapies is unknown in these environments. Therefore, the aim of this study is to examine the efficacy of NO in preventing neointimal hyperplasia in animal models of type II DM and metabolic syndrome and examine possible mechanisms for differences in outcomes. Aortic vascular smooth muscle cells (VSMC) were harvested from rodent models of type II DM (Zucker diabetic fatty), metabolic syndrome (obese Zucker), and their genetic control (lean Zucker). Interestingly, NO inhibited proliferation and induced G0/G1 cell cycle arrest to the greatest extent in VSMC from rodent models of metabolic syndrome and type II DM compared with controls. This heightened efficacy was associated with increased expression of cyclin-dependent kinase inhibitor p21, but not p27. Using the rat carotid artery injury model to assess the efficacy of NO in vivo, we found that the NO donor PROLI/NO inhibited neointimal hyperplasia to the greatest extent in type II DM rodents, followed by metabolic syndrome, then controls. Increased neointimal hyperplasia correlated with increased reactive oxygen species (ROS) production, as demonstrated by dihydroethidium staining, and NO inhibited this increase most in metabolic syndrome and DM. In conclusion, NO was surprisingly a more effective inhibitor of neointimal hyperplasia following arterial injury in type II DM and metabolic syndrome vs. control. This heightened efficacy may be secondary to greater inhibition of VSMC proliferation through cell cycle arrest and regulation of ROS expression, in addition to other possible unidentified mechanisms that deserve further exploration.     

Early endocrine and molecular changes in metabolic syndrome models

The twenty-first century arrived in the middle of a global epidemic of metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). It is generally accepted that an excess of nutrients linked to a low physical activity triggers the problem. However, the molecular features that interact to develop the MS are not clear. In an effort to understand and control them, they have been extensively studied, but this goal has not been achieved yet. Nonhuman animal models have been used to explore diet and genetic factors in which experimental conditions are controlled. For example, only one factor in the diet, such as fats or carbohydrates can be modified to better understand a single change that would be impossible in humans. Most of the studies have been done in rodents. However, it is difficult to directly compare them, because experiments are different in more than one variable; genetic strains, amount, and the type of fat used in the diet and sex. Thus, the only possible criteria of comparison are the relevance of the observed changes. We review different animal models and add some original observations on short-term changes in metabolism and beta cells in our own model of adult Wistar rats that are not especially prone to get fat or develop DM2, treated with 20% sucrose in drinking water. One early change observed in pancreatic beta cells is the increase in GLUT2 expression that is located to the membrane of the cells. This change could partially explain the presence of insulin hypersecretion and hyperinsulinemia in these rats. Understanding early changes that lead to MS and in time to pancreatic islet exhaustion is an important biomedical problem that may contribute to learn how to prevent or even reverse MS, before developing DM2.     

Tumour metabolomics in animal models of human cancer

Multinuclear Nuclear Magnetic Resonance Spectroscopy (MRS) and mass spectrometry (MS) are the key analytical techniques used in an increasing manner to explore tumor metabolite profiles. Recent work has revealed that metabolite profiles in various tumor preparations (i.e., cultured cells, tissue specimens, and tumors in vivo) show strong correlations with tumor type, proliferation, metabolic activity, and cell death. These data are regarded as highly promising for tumor diagnosis as well as assessment of prognosis and treatment response in a clinical setting. In this pursuit, animal models of human cancer have played a central role. In this short account, we review the potentials of MRS and MS techniques for animal tumor metabolomic work, as well as highlight some interesting applications of these techniques for various animal tumor types.     

Bile Acid Binding Resin Improves Metabolic Control through the Induction of Energy Expenditure

Background

Besides well-established roles of bile acids (BA) in dietary lipid absorption and cholesterol homeostasis, it has recently become clear that BA is also a biological signaling molecule. We have shown that strategies aimed at activating TGR5 by increasing the BA pool size with BA administration may constitute a significant therapeutic advance to combat the metabolic syndrome and suggest that such strategies are worth testing in a clinical setting. Bile acid binding resin (BABR) is known not only to reduce serum cholesterol levels but also to improve glucose tolerance and insulin resistance in animal models and humans. However, the mechanisms by which BABR affects glucose homeostasis have not been established. We investigated how BABR affects glycemic control in diet-induced obesity models.

Methods and Findings

We evaluated the metabolic effect of BABR by administrating colestimide to animal models for the metabolic syndrome. Administration of BABR increased energy expenditure, translating into significant weight reduction and insulin sensitization. The metabolic effects of BABR coincide with activation of cholesterol and BA synthesis in liver and thermogenesis in brown adipose tissue. Interestingly, these effects of BABR occur despite normal food intake and triglyceride absorption. Administration of BABR and BA had similar effects on BA composition and thermogenesis, suggesting that they both are mediated via TGR5 activation.

Conclusion

Our data hence suggest that BABR could be useful for the management of the impaired glucose tolerance of the metabolic syndrome, since they not only lower cholesterol levels, but also reduce obesity and improve insulin resistance.     

饮食诱导代谢综合征小鼠模型的建立

目的建立以高脂纯化饲料诱导的、遗传背景和环境因素共同起作用的C57BL/6J小鼠代谢综合征（MS）模型,为研究营养因素与代谢综合征的关系提供周期较短、稳定性好、可重复性、与人类发病可比性高的动物模型。方法雄性3周龄C57BL/6J小鼠30只适应性喂养10d后随机分为2组,其中一组（10只）给予普通生长饲料（对照组）,另一组（20只）给予高脂纯化饲料（模型组）。喂养期间对空腹血糖（FBG）、体重进行连续监测,同时监测体重指数（BMI）、血清胰岛素（FINS）、血清甘油三脂（TG）、总胆固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）,实验期10周。实验结束时取内脏脂肪和肝脏称重,取肝胰做病理分析。结果分组喂养1周时,模型组小鼠体重出现显著性升高（P〈0.001）,并表现为中心型肥胖。4周时FBG显著性升高（P〈0.05）,5周时FINS开始升高但无显著性差异。8周时血清TC、HDL-C显著性升高（P〈0.001）,10周时TG、TC、HDL-C、LDL-C均升高（P〈0.01）。HE染色显示肝脏中度脂肪变,胰岛细胞无明显改变。结论单纯施以高脂饲料10周即可建立MS小鼠模型。并且该模型造模方法简单易行、周期较短、稳定性好、可重复性高,与人类MS自然发病过程类似,是MS较理想的动物模型。     

Overview of growth differentiation factor 15 in metabolic syndrome

Growth and differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily. GDF15 has been linked with several metabolic syndrome pathologies such as obesity and cardiovascular diseases. GDF15 is considered to be a metabolic regulator, although its precise mechanisms of action remain to be determined. Glial cell-derived neurotrophic factor family receptor alpha-like (GRAL), located in the hindbrain, has been identified as the receptor for GDF15 and signals through the coreceptor receptor tyrosine kinase (RET). Administration of GDF15 analogues in preclinical studies using various animal models has consistently been shown to induce weight loss through a reduction in food intake. GDF15, therefore, represents an attractive target to combat the current global obesity epidemic. In this article, we review current knowledge on GDF15 and its involvement in metabolic syndrome.     

慢性阻塞性肺疾病与代谢综合征及颈动脉内膜厚度的相关性研究

目的:研究慢性阻塞性肺疾病与代谢综合征及颈动脉内膜厚度的关系。方法:选择2014年8月至2015年4月在我院就诊的慢性阻塞性肺疾病患者60例作为研究组,另选择同期在我院接受健康体检的60名志愿者作为对照组。比较两组空腹血糖、甘油三酯及高密度脂蛋白胆固醇水平、代谢综合征的发生率、颈动脉内膜厚度以及合并与不合并代谢综合征的慢性阻塞性肺疾病患者的肺功能和颈动脉内膜厚度,并采用多元回归分析颈动脉内膜厚度与慢性阻塞性肺疾病及代谢综合征的相关性。结果:与对照组相比,研究组患者空腹血糖(FPG)明显升高,而甘油三酯(TG)水平明显降低,差异具有统计学意义(P0.05);两组高密度脂蛋白胆固醇(HDL-C)比较差异无统计学意义(P0.05)。研究组代谢综合征的发病率、颈动脉内膜厚度均明显高于对照组,差异具有统计学意义(P0.05);慢性阻塞性肺疾病合并代谢综合征患者的肺功能明显优于无代谢综合征的慢性阻塞性肺疾病患者,差异具有统计学意义(P0.05);合并代谢综合征的慢性阻塞性肺疾病患者FEV1占预计值百分比及FEV1/FVC均明显高于无代谢综合征慢性阻塞性肺疾病患者的对应值,差异具有统计学意义(P0.05)。Logistic回归分析结果显示慢性阻塞性肺疾病与颈动脉内膜厚度呈独立相关性,而代谢综合征与颈动脉内膜厚度无直接相关性。结论:慢性阻塞性肺疾病与颈动脉内膜厚度呈独立相关,且慢性阻塞性肺疾病合并代谢综合征患者发生颈动脉粥样硬化的风险更高。