肺癌移植性动物模型的研究进展

目前在全球,肺癌发病率呈逐年上升趋势,近10余年来已成为癌症死亡原因之首,建立相应的肺癌模型有助于研究肺癌发生发展的机制,有助于找到治疗和防范肺癌的有效方法。肺癌移植性模型有较多优点,正处于不断的应用和发展中。     

The benefit of animal models for autoimmune hepatitis

Autoimmune hepatitis (AIH) is a chronic liver disease which is normally recognized during late stage of the disease. Due to limited knowledge about the onset and course of disease and need for chronic immunosuppression with significant side-effects there is a requirement for a good preclinical animal model, mirroring main characteristics of AIH. In addition to the exclusion of other liver diseases, AIH is characterized by elevated serum transaminases, specific autoantibodies and elevated gammaglobulins as well as a specific liver histopathology. A good preclinical model should mirror most of these criteria. In the last decades several models have been published using different approaches to break hepatic tolerance and induce liver damage. The induction of a chronic hepatitis similar to the human disease remained a difficult challenge. Nevertheless, these models helped to get more information about the aspects of AIH induction and liver immunology.     

建立创伤性气道狭窄动物模型的研究现状与进展

良性气道狭窄是呼吸介入领域的常见疾病,创伤性因素是气道狭窄形成的主要病因之一.建立气道狭窄动物模型对深入研究其发病机制与疾病防治具有主要意义.目前已有不少通过损伤气管壁的方法建立气道狭窄动物模型的研究报道.本文从实验动物、周期、方法及展望等方面,就建立创伤性气道狭窄动物模型的现状与研究进展作一综述.     

阻塞性睡眠呼吸暂停综合征动物模型的研究进展

阻塞性睡眠呼吸暂停综合征发病机制和病理生理复杂,研究主要依赖于动物模型的建立,目前尚缺乏理想的、稳定的、简单的动物模型,本文从动物的选择及模型建立的实验装置、模拟方式及模型的验证和应用方面对阻塞性睡眠呼吸暂停综合征动物模型作一综述.     

炎症性肠病的实验动物模型的研究进展

炎症性肠病(IBD)包括溃疡性结肠炎(UC)和克罗恩病(CD),是一类以反复复发和缓解为临床特征的疾病。UC和CD在西方国家较常见,在国内相对少见,但近年来报道其在国内发病率和患病率有增长趋势。IBD的病因和发病机制至今未明,但大多数学者认为IBD是由遗传、环境和免疫等多种因素共同作用所致。近年随着IBD实验动物模型的发展,IBD动物模型不仅为研发新药提供了基础也为研究其发病机制创造了条件。本文主要对化学药物诱导型动物模型、基因型动物模型、细胞移植型动物模型、自发性动物模型这4种实验动物模型的机制、建立方法、特征和应用作一综述。并且还概括了理想动物模型的特点、IBD发病机制、IBD动物模型与人类IBD的关系。     

炎症性肠病基因工程动物模型概述

炎症性肠病(IBD)具有遗传异质性,许多免疫调制分子基因的突变可导致炎症发生.转基因和基因敲除动物模型带动了自发性结肠炎动物模型的发展.基因工程动物模型的研究有利于建立新的假说并可能为IBD患者提供新的治疗方法.     

Immunohistological analyses of myocardial infiltrating cells in various animal models of myocarditis

Animal models of myocarditis are of great value for studying the pathophysiology of the disease. To clarify the key factors for determining the severity of myocarditis, we analyzed immunohistological surface markers of myocardial infiltrating cells in various animal models, and the relationship between myocardiogenic antigens and abnormal behaviours of infiltrating cells was discussed. Myocarditis was induced in mice and rats by cardiotropic viruses and by porcine cardiac myosin. Animals were sacrificed at the peak of their disease. Pathological examinations were performed, and the severity of the lesions was scored semiquantitatively. There were striking differences in the severity of viral and autoimmune giant cell myocarditis among different animal models. However, the majority of myocardial infiltrating cells were comprised of macrophages and CD4+ T cells. Different immunological behaviours of myocardial infiltrating cells were demonstrated in these models of myocarditis. However, the development of severe myocardial lesions may depend on the macrophage-CD4 cell lineage in these animal models.     

从Graves病动物模型看TSHR和TRAb

1996年Shimojo建立了Graves病(GD)动物模型后,开创了用表达促甲状腺激素受体(TSHR)的活体载体接种实验动物的新型GD动物模型。到目前为止,各种动物模型有其各自的优势和劣势,从不同模型中获得的信息远大于单一模型。对动物模型的研究证实,高度糖基化的TSHR的A亚单位启动或是增强了导致甲状腺功能亢进的免疫应答,TSHR氨基端在识别甲状腺刺激性抗体过程中具有重要作用。促甲状腺激素受体抗体(TRAb)的滴度水平和TSAb与TSH阻断性抗体(TBAb)的比例有关,这可能是抗体对免疫显性区的表位限制性所致。     

隐孢子虫感染模型及体外培养研究进展

隐孢子虫是一种重要的人兽共患寄生原虫,能引起婴幼儿和免疫低下人群及动物以胃肠道腹泻为主的严重消化道疾病。隐孢子虫动物感染模型和体外培养体系的建立,为隐孢子虫的生长发育过程、免疫学、疫苗研究、药物筛选和疗效考核以及卵囊灭活技术提供了良好的基础。本文就近年来隐孢子虫的动物感染模型和体外培养体系的发展及其应用情况作一综述。     

肺气肿动物模型研究进展

阻塞性肺气肿（肺气肿）是慢性阻塞性肺疾病（COPD）的主要病理表现,已成为研究中的焦点。多种实验性肺气肿动物模型的研究对揭示COPD的遗传背景、诱发因素、发病机制及新药的开发起了极大的促进作用。最近,有大量研究数据显示,细胞凋亡在COPD发病中起重要作用。本文就肺气肿动物模型的构建方法及其研究进展作一综述。     

Estradiol exerts neuroprotective actions against ischemic brain injury: insights derived from animal models

Over the last 100 yr, the life-span of women has increased from 50 yr to over 80 yr, but the age of the menopause has remained unchanged, at 51 yr. Menopause is one of the most permanent physiologic changes that a woman will experience and is marked by a dramatic decrease in circulating levels of ovarian estrogens. Because the timing of menopause has remained fixed in the face of an increasing life-span, more women will live a greater proportion of their lives in a hypoestrogenic state. We appreciate more and more that the actions of ovarian steroid hormones are complex, and possibly exert opposing actions in different contexts. I review here the results of my laboratory’s recent studies that clearly establish that low physiologic levels of estradiol replacement can exert profound neuroprotective actions when administered prior to an ischemic strokelike injury.     

常用糖尿病肾病动物模型研究概述

糖尿病肾病是糖尿病进展到晚期阶段的一种微血管并发症,大约有20%~40%的糖尿病患者晚期会进展为糖尿病肾病。在全世界范围内,糖尿病肾病已经成为终末期肾脏病的主要原因。动物模型是研究糖尿病肾病发病机制和治疗方法的良好工具。目前常用的糖尿病肾病模型,都在病理生理上不同程度地模拟了人类糖尿病肾病的部分特征。但糖尿病肾病的研究并未取得可观的进展,其阻碍主要是目前尚无能够完全模拟人类糖尿病肾病所有特征的有效动物模型。本文主要从造模机制、病理生理、优缺点等方面出发,对目前常用的糖尿病肾病动物模型作一综述。     

Comparison of cecal abrasion and multiple-abrasion models in generating intra-abdominal adhesions for animal studies

Abstract Background The formation of postoperative adhesions is a common problem in abdominal surgery that may lead to serious complications. Appropriate animal adhesion models are essential for the investigation of adhesiogenesis and the development of new anti-adhesive products. Although animal models have been developed to study the process of adhesion formation in the abdomen, they are not effective in generating adhesions located over small bowel where adhesions are most commonly observed in clinical practice. Methods Twenty-nine Sprague Dawley rats were subjected to standardized cecal abrasion (group 1; n=9), or two types of multiple abrasion, in which cecal and 3 or 5 abrasions were performed on small bowel (group 2, n=10; and group 3, n=10). An observer blinded to the randomization assessed the difficulty of adhesiolysis on a 6-point scale, and the locations of the adhesions were recorded 21 days after the initial surgery. Results Adhesiolysis was significantly more difficult in group 3 than in group 1 (p=0.01). The number of animals that had adhesions between the small bowel segments and the total number of locations where small bowel adhered were significantly greater in group 2 and 3 than in group 1 (p<0.05 for all comparisons). Conclusions Abrasions to the small bowel created consistent adhesions that have clinical characteristics of intra-abdominal adhesions as compared to the standard cecal abrasion model and that can be used in future animal studies on adhesions.     

Molecular genetics of AMD and current animal models

During the past few years systematic investigation into the epidemiology, genetics, and pathophysiology of age-related macular degeneration (AMD) has provided important new insight into this leading cause of vision loss in older persons. These studies provide a view of AMD as a complex trait influenced by well-established genetic and environmental risks that leads to the deposition of inflammatory deposits in the outer retina. This maculopathy leads to visual dysfunction through a variety of mechanisms and complications that can be observed in both humans and animal models. In this review, the risks associated with AMD in humans and the animal models used to study AMD and its complications will be summarized. No effort has been made to perform a comprehensive citation of all areas of AMD genetics and animal models, but rather a selection of observations and supporting references illustrative of the current state of the field is presented.     

化疗致胃肠道黏膜炎动物模型构建方法的研究进展

化疗后胃肠道黏膜炎的主要问题之一是其根本的发病机制尚未完全阐明,研究者无法直接在人体上开展实验,难以制定有效干预措施.动物模型的应用在该领域的研究中起到极为关键的作用.近年来,研究者通过复制接近人体状态的动物模型,在各类化疗药物的细胞机制和临床药理学研究方面取得了显著进展.本文通过MeSH主题词结合自由词,电子检索PubMed(1950-2011)、Science Direct(1823-2011)数据库,对荷瘤大鼠化疗胃肠黏膜炎模型、胃肠黏膜炎非荷瘤模型、基因敲除和转基因动物模型进行综述,全面分析各种化疗后胃肠道黏膜炎模型的造模方法及优缺点,为今后研究化疗的胃肠黏膜毒性反应及其机制,提供造模方面的选择和参考依据.     

沙眼衣原体生殖道感染动物模型的研究进展

沙眼衣原体生殖道感染可以引起性传播疾病,建立沙眼衣原体生殖道感染的动物模型,是了解其致病机制、新药研发及疫苗研制的重要手段。目前主要使用不同型别沙眼衣原体或鼠衣原体模拟沙眼衣原体建立动物模型。用于沙眼衣原体生殖道感染动物模型的动物有：小鼠、灵长类动物、豚鼠、猪等,而小鼠感染动物模型是众多模型中较为经济且易于操作的模型。     

慢性阻塞性肺疾病动物模型构建及评价

COPD是一种可以预防和治疗的疾病。多种实验性COPD动物模型对揭示COPD的遗传背景、诱发因素、发病机制及新药的开发提供了良好的研究平台。本文就COPD动物模型的构建及其研究进展作一综述。     

人芽囊原虫感染动物模型构建研究进展

人芽囊原虫是一种常见的寄生于人和动物肠道内的寄生原虫,其致病性尚有争议.构建动物模型对于研究人芽囊原虫致病性、致病机制以及药物筛选等具有重要意义.实验动物、感染方式和虫体选择以及宿主免疫状态是影响人芽囊原虫感染动物模型构建的重要因素.本文综述了近年来人芽囊原虫感染动物模型的相关研究进展,阐述了构建人芽囊原虫感染动物模型...     

Lessons from animal models of NASH.

Studies of animals with obesity-related liver disease have taught us much about the mechanisms that mediate this pathology. Our work with genetically obese, insulin-resistant ob/ob mice demonstrates that hepatocytes become steatotic and die at increased rates. Thus, ob/ob mice develop non-alcoholic steatohepatitis (NASH) spontaneously. NASH is intimately related to the insulin resistance (i.e., metabolic) syndrome, a constellation of disorders that result from abnormal production of hormones and cytokines that regulate inflammatory responses. Like humans with the metabolic syndrome, ob/ob mice exhibit increased tumor necrosis factor (TNF) but relatively low levels of adiponectin. Because TNF and adiponectin typically antagonize each other, the combination of increased TNF and decreased adiponectin promotes a state of high TNF activity. Consequently, hepatocytes generate excessive reactive oxygen species (ROS), have altered viability, accumulate lipid and are resistant to insulin. Treatments that inhibit TNF activity or that increase adiponectin improve NASH in ob/ob mice, other mice and humans with NASH. Hence, there is no doubt that cytokine and hormonal imbalances play a key role in the pathogenesis of NASH. However, the fundamental cellular events involved are still poorly understood. Even within very small areas of livers with NASH, most hepatocytes are merely steatotic, while others are ballooned (pre-necrotic), and still others have succumbed to apoptosis. This observation suggests cell-to-cell variability in the response to chronic inflammatory stress. In NASH, most steatotic hepatocytes survive by inducing adaptive, cytoprotective factors. However, such cells respond to super-imposed toxic and mitogenic stimuli differently than (3)na?ve(2) (un-adapted) hepatocytes. Fatty hepatocytes tend to be more vulnerable to ATP depletion and less proliferative, perpetuating chronic liver injury while encouraging the expansion of liver progenitor populations that may become neoplastic. Finally, like other causes of chronic injury, NASH increases the risk for cirrhosis. Studies of ob/ob mice demonstrate that progression to cirrhosis is potentiated by leptin. Leptin probably acts at multiple levels to promote hepatic fibrosis, including direct activation of stellate cells via leptin receptors, regulation of pro- and anti-fibrogenic cytokine production by innate immune cells, and modulation of other neuronal factors that regulate stellate cell activation. The latter two mechanisms seem to dominate because stellate cell activation, fibrogenic cytokine production, collagen gene expression and fibrosis can all be induced by manipulating cytokines and neuronal factors in ob/ob mice (that are genetically deficient in leptin). Thus, studies in mice have uncovered several basic mechanisms that explain the dysfunction that occurs in different types of liver cells during the metabolic syndrome. This has important therapeutic implications for human NASH.     

变应性鼻炎动物模型的研究进展

变应性鼻炎是一种变态反应性疾病,是全身变应性炎症的局部反应,发病率高,发病机制复杂,因此,建立能够较好的模拟人类变应性鼻炎的动物模型有助于对其发病机制和治疗进行深入研究.目前,已经建立了多种变应性鼻炎的动物模型.本文就用各种动物建立的变应性鼻炎模型作如下综述.