莱姆病实验动物模型研究

用从我国新疆全沟硬蜱分离培养的莱姆病螺旋体(XS3),实验感染了新西兰白兔、大耳白兔、13号鼠、大白鼠、中国地鼠、金黄地鼠和豚鼠等7种动物。在一只新西兰白兔发现慢性游走性红斑,一只金黄地鼠和一只13号鼠产生关节炎。患病动物都有较高滴度的抗体。这些结果证实。(1)我国全沟硬蜱莱姆病螺旋体具有足够致病的能力;(2)经培养传代的螺旋体的毒力是稳定的,可引起实验动物莱姆病;(3)莱姆病的发病机理可能与免疫应答有关。另外,证实血中螺旋体的浓度较低,持续时间较短。     

Osteopetrosis: from Animal Models to Human Conditions

The term “osteopetrosis” is applied to a group of disorders characterized by an increased bone density, due to an inadequate bone resorption. A considerable part of our current knowledge on osteoclast biology is based on the study of osteopetrotic animal models. The search for mutations in these animals has unveiled many molecular mechanisms underlying osteoclast differentiation and functioning. It also supplied new candidate genes for the identification of genes involved in the human variants of this disease. All osteopetrotic genes identified so far in humans have their animal counterpart. The reverse is not true. This can partially be explained by the fact that still more than 30% of all patients suffer from osteopetrosis with an unkown molecular defect. Therefore, the studies of the osteopetrotic animal models and the correlating human osteopetrotic forms were and are still very important for our knowledge of the aetiology, prognosis and treatment of this disease. This review focuses on osteopetrotic animal models as well as human osteopetrotic conditions and their impact on osteoclast biology, pathogenesis and treatment.     

炎症性肠病动物模型研究进展

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）。目前IBD的确切病因和发病机制尚不清楚。相当一部分IBD的研究成果源于动物模型的研究,因此建立合适的动物模型至关重要。本文就几种常用的IBD实验动物模型作一综述。     

Proteomics in Inflammatory Bowel Disease: Approach Using Animal Models

Recently, proteomics studies have provided important information on the role of proteins in health and disease. In the domain of inflammatory bowel disease, proteomics has shed important light on the pathogenesis and pathophysiology of inflammation and has contributed to the discovery of some putative clinical biomarkers of disease activity. By being able to obtain a large number of specimens from multiple sites and control for confounding environmental, genetic, and metabolic factors, proteomics studies using animal models of colitis offered an alternative approach to human studies. Our aim is to review the information and lessons acquired so far from the use of proteomics in animal models of colitis. These studies helped understand the importance of different proteins at different stages of the disease and unraveled the different pathways that are activated or inhibited during the inflammatory process. Expressed proteins related to inflammation, cellular structure, endoplasmic reticulum stress, and energy depletion advanced the knowledge about the reaction of intestinal cells to inflammation and repair. The role of mesenteric lymphocytes, exosomes, and the intestinal mucosal barrier was emphasized in the inflammatory process. In addition, studies in animal models revealed mechanisms of the beneficial effects of some therapeutic interventions and foods or food components on intestinal inflammation by monitoring changes in protein expression and paved the way for some new possible inflammatory pathways to target in the future. Advances in proteomics technology will further clarify the interaction between intestinal microbiota and IBD pathogenesis and investigate the gene-environmental axis of IBD etiology.     

N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus

The first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. Over 50 different sialic acid modifications are known, of which N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two main species. Animal models with α2,6 linked Neu5Ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza A viruses. Animal models that are currently most often used to study human influenza are mice and ferrets. Additionally, guinea pigs, cotton rats, Syrian hamsters, tree shrews, domestic swine, and non-human primates (macaques and marmosets) are discussed. The presence of NeuGc and the distribution of sialic acid linkages in the most commonly used models is summarized and experimentally determined. We also evaluated the role of Neu5Gc in infection using Neu5Gc binding viruses and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)^−/− knockout mice, which lack Neu5Gc and concluded that Neu5Gc is unlikely to be a decoy receptor. This article provides a base for choosing an appropriate animal model. Although mice are one of the most favored models, they are hardly naturally susceptible to infection with human influenza viruses, possibly because they express mainly α2,3 linked sialic acids with both Neu5Ac and Neu5Gc modifications. We suggest using ferrets, which resemble humans closely in the sialic acid content, both in the linkages and the lack of Neu5Gc, lung organization, susceptibility, and disease pathogenesis.     

Animal Models of Dyssynchrony

Cardiac resynchronization therapy (CRT) is an important therapy for patients with heart failure and conduction pathology, but the benefits are heterogeneous between patients and approximately a third of patients do not show signs of clinical or echocardiographic response. This calls for a better understanding of the underlying conduction disease and resynchronization. In this review, we discuss to what extent established and novel animal models can help to better understand the pathophysiology of dyssynchrony and the benefits of CRT.     

Animal Models of Osteonecrosis

Osteonecrosis is an uncommon but significant musculoskeletal disease characterized by focal areas of dead bone that often fail to heal even with intervention and has the potential to negatively impact a patient’s quality of life. The knee and hip seem to be most susceptible to osteonecrosis although certain conditions, such as bisphosphonate treatment, have been associated with the development of osteonecrosis that is confined to the jaw. For most types of osteonecrosis, there remains much to be learned about either the pathophysiology of disease or the best course of treatment—questions that are best approached using an animal model. The different etiologies of the subclasses of osteonecrosis have led to a diverse number of animal models within the field. While no one animal model completely simulates all aspects of a particular type of osteonecrosis, models do exist that mimic various clinical aspects of osteonecrosis. This review discusses aspects of the common and novel animal models used to study juvenile osteonecrosis (Legg-Calvé-Perthes), trauma-induced osteonecrosis, alcohol- and corticosteroid-induced osteonecrosis, and osteonecrosis of the jaw associated with anti-remodeling drug treatment.     

Animal Models For Osteoporosis

Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.     

系统性硬化症动物模型

系统性硬化症是一种自身免疫病,以多系统纤维化、小血管病变、血清自身抗体阳性为主要特点。目前其病因尚未十分清楚,越来越多的证据显示可能有血管病变、炎性反应、纤维化、自身免疫四大机制参与并相互作用。在研究系统性硬化症的发病机制、探索新药治疗效果时需要用到动物模型来模拟病理生理过程,而每一种模型都有其特点却又不完美。本文将根据建模方法分类介绍一些经典的和创新的模型,以及它们各自的特点、应用价值,为研究者选择最合适的动物模型提供帮助。     

冠状动脉再狭窄的动物模型

在冠脉支架应用的时代,再狭窄仍然制约着经皮冠脉介入治疗。许多动物模型被用于研究冠状动脉再狭窄的病理生理机制,并探讨其防治途径。现就近年来冠脉再狭窄动物模型研究的相关进展作一综述。     

Animal Models of Inflammatory Myopathy

The idiopathic inflammatory myopathies (IIMs) represent a heterogeneous group of disorders characterized by mononuclear cell infiltration of muscle and varying degrees of muscle dysfunction. To better understand the pathogenesis of these diseases, investigators have devised a number of infectious, genetic, and antigen-induced animal models that replicate different aspects of muscle involvement. Although the underlying heterogeneity of disorders encompassed by IIM precludes development of a single unifying model, several recently developed experimental systems have provided tremendous insight regarding the contributions of both immune- and non–immune-mediated disease pathways in various subsets of IIM. In turn, by elucidating the pathogenic roles of such disparate factors as endoplasmic reticulum stress and innate immune signaling, these models have established the foundation for more novel, targeted therapeutic intervention.     

正确选择炎症性肠病实验研究的动物模型

炎症性肠病（inflammatory bowel disease，IBD）是一种反复发作的慢性非特异性肠道炎症性疾病。主要包括溃疡性结肠炎（ulcerative colitis，UC）和克罗恩病（Crohn’s disease，CD）。其确切病因和发病机制至今尚未阐明，治疗上也缺乏特异有效的药物旧。因此，为研究其病因和发病机制以及开发新的治疗药物．建立理想的、类似于人类IBD的动物模型就显得非常重要。理想的IBD实验动物模型应具备如下特点：①肠道炎症的发生、病程、病理和病理生理学改变与人类IBD相同或相似；②实验动物具有明确的遗传背景：③以已知抗原易于诱导免疫反应；④传统IBD治疗药物治疗有效；⑤实验动物在没有遗传或化学药物干预的情况下。常能自发形成肠道炎症。然而，实际上很少有如此理想的动物模型。应当明确的是，目前所建立的所有IBD动物模型都不是真正意义上的IBD动物模型．而只能称为肠道炎症模型。     

Experimental Colitis in Animal Models

Despite extensive research on their immunologic, biochemical, microbiologic, and epidemiologic aspects, the etiology and pathogenesis of ulcerative colitis and Crohn's disease (inflammatory bowel disease (IBD)) are still not known. Consequently, the therapeutic approach remains empiric. Nor do we know the ideal animal model for study of IBD. Nevertheless, important insight into the nature of the human disease may be obtained from the study in animals. In this article we discuss pathogenetic mechanisms of experimental colitis in various animal models.

SUMMARY

Colitis may be induced in animals by oral administration of sulfated polysaccharides (carrageenan, amylopectin sulfate, dextran sulfate), chemical irritation by rectal instillation of sensitization to DNCB or after one single administration of TNBS, and Arthus reaction induced by intravenous injection of immune complexes after chemical irritation of the colon, and by chemoattractant peptides such as FMLP. It appears rabbit produce increased amounts of eicosanoids similar to that found in human colitis. Thus, animal studies provide useful information on the origin, regulation, and function of inflammatory mediators. However, with the possible exception of the cotton-top tamarin, no animal model of induced or spontaneous inflammation of the colon is analogous to human ulcerative colitis in etiology, course of disease activity, or histology (114).

The observation that two different immune-mediated models gave similar results suggests that the colitis is not a specific response to delayed-type hypersensitivity or immune-complex-mediated reactions but rather an unspecific, stereotype response (125). The original disturbance may not determine the nature of the lesions ultiniately produced but may instead serve as an initiator of a final common immunologic pathway.