模型猪应用于人类肥胖研究的可行性

肥胖会引起机体代谢不正常进而引发一系列代谢综合疾病。目前肥胖的潜在分子机理和生物分子机制研究进展比较缓慢,其中的一个重要瓶颈就是动物模型的选择。为探索模型猪应用于人类肥胖研究的可行性,从基因组进化和生理学上分析了模型猪应用于人类肥胖研究的优势,提出了啮齿类动物模型的局限性,概述了模型猪用于人类肥胖研究的进展。猪的基因组与人类的相似度约为60%,代谢系统模式与人类也十分相似,且在消化生理机能、饮食习惯、器官大小和脂肪组织分布上具有高度的相似性,相比常用的啮齿类动物模型,模型猪具有更高的人类肥胖研究优势,且已有很多利用模型猪开展人类肥胖疾病预防和治疗的研究并取得了一定进展,因此模型猪将会是人类肥胖疾病研究的一个可靠选择。本文为人类肥胖研究的模型动物选择提供了更多思路。     

我国实验动物——小型猪资源

随着医学和医药学研究领域的不断发展,实验动物作为医学研究的辅助手段也在不断地进步,除了常规的犬、鼠、兔、猴等常规实验动物外,由于猪的各种生理生化等医学指标与人类很接近,不仅步人了实验动物领域,而且正在被广泛应用于疾病模型、皮肤与器官移植等领域.那么,我国有哪些猪种可以作为实验动物呢?本文将对此做一概述.     

农大小型猪的选育

<正> 小型猪主要作为实验动物,服务于生物、药物、医学等科研领域,选育的目标是:体型小,生长慢,抗病强,健康无病。猪的血液、淋巴、激素、尿、代谢等诸多项生理生化常值及营养代谢与人类有极大的相似性,这便具备了成为人类医学、疾病模型、口腔医学及外科医学等领域研究的实     

猪作为人类传染病模型动物的研究进展

作为人类传染病研究的模型动物必须能够准确地再现疾病的各个方面。从解剖学、遗传学及生理学的角度看,家猪与人类极为相似,是一种可用于研究各种微生物感染性疾病的理想动物模型。研究发现,相比于啮齿类动物,以猪作为模型动物能更准确地预测人类疾病的治疗方法。在本综述中,我们将重点阐述在人类传染病研究及疫苗研发过程中猪作为模型动物的种种优势,以及人们从中获得的众多关于提高动物和人类健康的新知识。     

猪生物医学模型的基因组学研究进展

本综述对猪生物医学模型的多样性和基因组学在这些模型持续开发中的重要性作了一个简要的更新。由于猪在体型大小、生理条件、器官发育和疾病发展等方面与人类相似,因而已作为一种重要的哺乳动物医学模型为人类所用。将猪作为人类医学模型,可以使研究人员从容不迫地安排研究时间,并可利用普通的人类医学技术对机体内部的血管和器官进行成像处理,且可以采集重复的外周样本,并且在扑杀后可采集复杂的粘膜组织样本。以猪为医学模型,能够利用同窝的猪或克隆猪和转基因猪,因而使比较分析和遗传作图更为容易。以猪作为人类医学的动物模型可获得大量代表各种组织的分化方向明确的细胞系,从而可更加有利于基因表达和药物敏感性的检测。因此,对人而言,猪是一种出色的生物医学模型。由于猪在基因序列和染色体结构上与人类高度同源,因而对基因组应用而言,其不失为一个宝贵的资源。由于目前猪基因组序列已被人类充分掌握,因而有改良型遗传学方法和蛋白质组学方法可供这些比较分析方法所利用。本综述将论述用于探测这些模型的基因组学方法中的某些方法,并将重点介绍黑色素瘤和抗传染性疾病的基因组学研究情况,论述在设计此类研究时应予以考虑的问题。本文最后将对利用基因组学方法开发控制具有最高经济价值的猪病—猪繁殖与呼吸综合征病毒(Porcine Reproductive and Respiratory Syndrome,PRRSV)—新型替代方法的可行性、和将从PRRSV研究中获得的知识应用到人传染性疾病研究中的可行性作简短讨论。     

小型猪生长模型的研究

小型猪是一种重要的实验动物,它与人类有非常相似的解剖生理特征,特别适用于人类医学中新药的安全评价、外科手术的利用和疾病模型的构建.小型猪的主要特征是体形小、体重轻,其优越性在于饲养费用少、育种成本低、生物医药研究中便于操作.近几十年来,小型猪作为生物医药材料的研究颇多(张德福,2004),但研究它的生长特征近几年才开始活跃起来(K(o)hn,2007).为此,笔者就小型猪的生长模型研究作一简要报道.     

昆明动物所在猪lincRNA基因DNA甲基化研究中取得新进展

<正>猪和人类有相似的心血管系统、代谢特征和器官大小。因此,近些年猪逐渐成为研究能量代谢、人类肥胖和器官移植的理想医学动物模型。数千年的人工选择已经使家猪具有了巨大的表型多样性,例如,不同的品种猪的脂肪和肌肉含量有很大的差异。因此,这些品系是研究脂肪沉积和肌肉发育的很好的模型。LincRNA是一类长链非编码RNA,在包括转录调控的多个生物学过     

昆明动物所在猪lincrna基因dna甲基化研究中取得新进展

<正>猪和人类有相似的心血管系统、代谢特征和器官大小。因此,近些年猪逐渐成为研究能量代谢、人类肥胖和器官移植的理想医学动物模型。数千年的人工选择已经使家猪具有了巨大的表型多样性,例如,不同的品种猪的脂肪和肌肉含量有很大的差异。因此,这些品系是研究脂肪沉积和肌肉发育的很好的模型。Linc RNA是一类长链非编码RNA,在包括转录调控的多个生物学     

医用小型猪选育方法和应用进展

模式动物广泛应用于人类疾病研究中。随着人类医学研究的深入，啮齿动物、犬、猴等经典模式动物不能完全满足科学研究的需要，而小型猪逐渐成为现有医用模式动物的有效补充。本文介绍了小型猪的基本生物学特性(包括解剖学和生理学特点),论述小型猪作为医用模式动物的优势和价值。同时，介绍了国内外18种不同品种小型猪的主要特征、产地、选育方式、应用进展等情况。此外，本文也回顾分析了目前以小型猪作为模式动物，在心血管、代谢、异种移植等领域的应用现状，以期为中国小型猪的种质资源保护、开发为医用模式动物提供参考，进而助力人类疾病研究。     

巴马小型猪动物模型在医学领域的研究进展

巴马小型猪是中国原产地闭锁繁殖的优质品种,具有遗传稳定性、理想的毛色分布、体型小、多产性、饲养要求低、抗病力强等优势,且在生理学、解剖结构、药物代谢、生化指标和疾病发生机制等方面与人类相似,已用于心血管、皮肤整形、内分泌及代谢、消化、口腔医学、异种移植、中医、麻醉学、神经系统等广泛医学领域的研究,建立了心肌缺血、冠脉微栓塞、卵圆孔未闭、动脉粥样硬化、皮肤创伤、经皮给药、代谢综合征、糖尿病及其并发症、梗阻性黄疸、慢性胰腺炎、肝硬化、肝脏射频消融、牙周组织炎症、下颌骨缺损、异种器官/细胞移植、中医征候、手术麻醉、脑缺血、支架植入、休克等一系列类似于人类疾病的动物模型,表明巴马小型猪作为理想的试验动物在生物医学研究中具有广阔的应用前景。作者综述了巴马小型猪作为试验动物在各医学领域的应用进展,了解现有巴马小型猪疾病模型的种类、构建方法及病理特征,有助于进一步探索具体的病因、发病机制、并发症和防制手段等,为拓展研究范围、提高医学水平奠定了科学基础。     

Adipokines: a review of biological and analytical principles and an update in dogs,cats, and horses

Abstract: In addition to its role as an energy storage depot, adipose tissue is now recognized as a complex endocrine organ. Adipose tissue releases a variety of factors, termed adipokines, that regulate energy metabolism, cardiovascular function, reproductive status, and immune function. Some of the better‐studied adipokines include leptin, adiponectin, and components of the renin‐angiotensin system such as angiotensinogen. The function of more recently discovered adipokines such as resistin are under intense scrutiny. Abnormal production or regulation of adipokines occurs in obese individuals and is implicated in the development of a variety of associated co‐morbidities including metabolic syndrome, type 2 diabetes, atherosclerosis, heart disease, and cancer in people, although evaluation in domestic species is just beginning. Adipokines are now being examined as potential biomarkers for risk assessment for development of complications related to obesity. This article summarizes the function and regulation of some better‐characterized adipokines. It also reviews the current information on the characterization of adipokines in some domestic species in which rates of obesity and obesity‐related disorders are increasing, such as the dog, cat, and horse.     

Is the metabolic syndrome a useful clinical concept in dogs? A review of the evidence

The metabolic syndrome is a set of risk factors for the development of type 2 diabetes, atherosclerosis, coronary heart disease and stroke in human beings. The term has recently been applied to dogs that exhibit components of the human metabolic syndrome, specifically visceral obesity, hypercholesterolaemia, hypertriglyceridaemia, hypertension and fasting hyperglycaemia. Obese dogs, like obese humans, are known to develop resistance to the glucose-lowering effects of insulin, and develop increased circulating concentrations of triglycerides, cholesterol and blood pressure. Unlike humans, however, obese dogs do not develop fasting hyperglycaemia or atherogenic hyperlipidaemia. Importantly, there is no evidence that dogs develop type 2 diabetes. Atherosclerosis, coronary heart disease and stroke are rare and not known to be associated with obesity in dogs. On the basis of current knowledge, the use of the term ‘metabolic syndrome’ in dogs does not appear to have merit.     

猪生物医学模型研究进展

猪与人不仅在体重、生理特点、器官形成和疾病的发生方面都有高度的相似性,而且二者在基因组序列和染色体结构上有很高的同源性,所以猪已被作为人类研究中最主要的哺乳动物模型.目前,小型猪已被广泛应用于皮肤烧伤、肿瘤、免疫学、心血管病、糖尿病、畸形学和产期生物学、牙科、药理学等多方面的模式研究,以及对黑色素瘤和感染性疾病的基因组学研究中.在控制猪繁殖与呼吸系统综合征发生中的一些可行的基因组学方法,将为人类相似的病毒感染性疾病研究提供重要的参考.     

Orosomucoid expression profiles in liver,adipose tissues and serum of lean and obese domestic pigs,Göttingen minipigs and Ossabaw minipigs

The acute phase protein orosomucoid (ORM) has anti-inflammatory and immunomodulatory effects, and may play an important role in the maintenance of metabolic homeostasis in obesity-induced low-grade inflammation. Even though the pig is a widely used model for obesity related metabolic symptoms, the expression of ORM has not yet been characterized in such pig models. The objective of this study was to investigate the expression of ORM1 mRNA in liver, visceral adipose tissue, subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal abdominal adipose tissue (RPAT) and SAT from the neck, as well as the serum concentration of ORM protein in three porcine obesity models; the domestic pig, Göttingen minipigs and Ossabaw minipigs.No changes in ORM1 mRNA expression were observed in obese pigs compared to lean pigs in the four types of tissues. However, obese Ossabaw minipigs, but none of the other breeds, showed significantly elevated ORM serum concentrations compared to their lean counterparts. Studies in humans have shown that the expression of ORM was unchanged in adipose tissue depots in obese humans with an increased serum concentration of ORM. Thus in this respect, obese Ossabaw minipigs behave more similarly to obese humans than the other two pig breeds investigated.     

动物脂肪沉积的分子调控机制

脂肪组织一直被当作具有能量的储存功能,直到一系列的脂肪细胞因子被发现后,人们逐渐认识到脂肪组织还是一个复杂且高度活跃的分泌功能,其参与包括食欲、能量平衡、胰岛素敏感性、繁殖、骨形成、炎症反应和免疫等许多过程的调控。脂肪功能的紊乱多与人类的肥胖病、糖尿病以及代谢综合症相关联,因此动物脂肪沉积的分子调控机制也备受人们关注。本文综述了目前在模式动物上研究的相对较为透彻的一些调控通路以及调控因子,例如,PPARg,C/EBPs,Hedgehog,Wnt/beta-catenin,BMPs,KLFs,Insulin和IGF1等。在未来的研究中,除了要继续利用模式动物挖掘和细化脂肪细胞分化的调控机制外,研究家畜脂肪组织调控机制的异同,对于动物育种也具有重要的意义。     

Oxidation, antioxidants and cataract formation: a literature review

PURPOSE: This review aims to provide a literature survey of the association between photo-oxidation of lens proteins and lipid peroxidation with the genesis of age-related cataract in laboratory studies using rodent models, in epidemiological and interventional studies in humans. MATERIALS AND METHODS: A Medline search using initial search terms lens, oxidation, antioxidant, and diet was employed to search for research papers covering the areas noted above from 1995 to 2005. Literature cited in those papers was also reviewed to provide as comprehensive a coverage of research work as possible. RESULTS: Lens protein photo-oxidation and lipid peroxidation are widely acknowledged as important steps in age-related cataractogenesis. Dietary antioxidants are central in retarding cataractogenesis, although most evidence for this is gained from laboratory-based work on relatively unphysiologic rodent cataract models, using antioxidant regimes that could not be sustained in clinical practice. Most research in humans is retrospective epidemiology although some interventional research has been undertaken, with mixed results. CONCLUSIONS: Dietary antioxidants are likely to be important in retarding cataractogenesis in older animals and in humans. Work on companion animals could provide a valuable stepping stone between rodent-based laboratory work and human interventional studies.     

Public health aspects of dirofilariasis in the United States

Coin lesions in the human lung present significant differential diagnostic problems to the physician. There are at least 20 known causes of such lesions, including neoplastic lesions, infectious diseases, and granulomas. The human medical literature contains many misconceptions about the life cycle of Dirofilaria immitis, including the method of entry of the infective-stage larvae and the development of the young adult worm. These misconceptions have obscured the recognition of the clinical presentation of pulmonary dirofilariasis and the potential for D. immitis to lodge in many other areas of the human body besides the lung. Exposure to infective larvae of D. immitis is more common in humans than is currently recognized. Reported cases in humans reflect the prevalence in the canine population in areas of the United States. The veterinary literature provides compelling evidence that D. immitis is a vascular parasite, not an intracardiac one. Its presence in the right ventricle is a post-mortem artifact, because it has never been shown to be there by echocardiography or angiography in a living dog, even though these techniques have demonstrated adult D. immitis in the pulmonary, femoral, and hepatic arteries; posterior vena cava; and right atrium of live dogs. Physicians have taken the name "heartworm" literally, believing that the worm lives in the heart and only after it dies does it embolize to the pulmonary artery. However, the coin lesion is spherical in shape, not pyramidal, as embolic infarcts to the lung in humans are known to be. The coin lesion is an end-stage result of the parasite's death in the vascular bed of the lungs and the stimulation of a pneumonitis followed by granuloma formation. This pneumonitis phase of human pulmonary dirofilariasis is often not recognized by the radiologist because of the way pneumonitis is diagnosed and treated and because the developing nodule is obscured by the lung inflammation. Serologic methods for use in humans are needed for clinical evaluations of patients with pneumonitis living in highly enzootic D. immitis regions. As well, epidemiological surveys are needed to determine the real extent of this zoonotic infection.     

The Gastrointestinal Microbiome: A Review

The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology. Recent advances in DNA sequencing technology and computational biology have revolutionized the field of microbiomics, permitting mechanistic evaluation of the relationships between an animal and its microbial symbionts. Changes in the gastrointestinal microbiome are associated with diseases in humans and animals including inflammatory bowel disease, asthma, obesity, metabolic syndrome, cardiovascular disease, immune‐mediated conditions, and neurodevelopmental conditions such as autism spectrum disorder. While there remains a paucity of data regarding the intestinal microbiome in small animals, recent studies have helped to characterize its role in host animal health and associated disease states. This review is intended to familiarize small animal veterinarians with recent advances in the field of microbiomics and to prime them for a future in which diagnostic tests and therapies will incorporate these developments into clinical practice.     

The cellular Toll-like receptor 4 antagonist E5531 can act as an agonist in horse whole blood

Sepsis and endotoxaemia are important causes of morbidity and mortality in humans. Research on sepsis focuses on rodent models most of which are poorly responsive to lipopolysaccharide (LPS), and thus do not mimic very well the high sensitivity of humans. Therefore, there is a need to develop more clinically relevant models. Horses suffer from a similar endotoxaemic syndrome to humans with high morbidity and mortality. LPS analogues that act as antagonists at Toll-like receptor 4 (TLR4) are being developed as novel treatments for endotoxaemia. Due to differences in recognition of ligands by TLR4 from different mammalian species, individual LPS molecules may act as agonists in some species and antagonists in others. The synthetic lipid A analogue E5531 is an antagonist at TLR4 in humans and mice, but its effects at TLR4 from other species are unknown. In the studies reported here, Escherichia coli LPS is a full agonist on equine bone marrow macrophage-like cells and its effects are antagonised by E5531. Similarly, E. coli LPS is an agonist and E5531 an antagonist on monocytes isolated from peripheral blood of healthy horses and human embryonic kidney (HEK) cells, transiently transfected to express horse TLR4 and its associated cell surface proteins MD2 and CD14. In contrast, both E. coli LPS and E5531 behave as agonists in horse whole blood by inducing production of equivalent amounts of the inflammatory mediator prostaglandin. This finding suggests that modification of E5531 may occur in whole blood, for example, deacylation, which alters its activity. This comparative study has revealed a novel pharmacological action of E5531 and emphasises the importance of extending studies of this nature beyond the normal rodent models.