类风湿关节炎动物模型与临床的关系

类风湿关节炎 (rheumatoidarthritis,RA)动物模型特别是大鼠佐剂性关节炎模型和小鼠胶原诱导性关节炎模型与人RA在发病机制、临床表现等有着相似的特点 ,是研究RA、筛选抗炎免疫药物较理想的病理模型。探讨RA动物模型的发病机制及其与临床的关系 ,对进一步了解RA的病理、生理、神经内分泌免疫等特点 ;对寻找安全有效的治疗RA的药物十分重要。该文就几种RA动物模型的建立、病理特征、临床表现等方面进行了论述     

类风湿性关节炎动物模型研究进展

类风湿性关节炎（rheumatoid arthritis,RA）是一种自身免疫性疾病,其病理机制不确定,目前治疗方法较多,但是多有副作用。关于RA的研究,构建和应用合适的动物模型是重要的一个环节,尤其是获得与人RA发病相似的动物模型尤为重要。目前研究表明,各种类风湿性关节炎模型的发病因素不同,病理特点有别,有必要对动物模型进行总结。     

实验性关节炎动物模型建立及病理机制研究进展

类风湿关节炎(rheumatoid arthritis,RA)是一种慢性系统性的免疫性炎症疾病,病因和发病机制尚未完全清楚。胶原性关节炎大鼠、小鼠模型,佐剂性关节炎大鼠模型,多聚糖蛋白诱导的关节炎小鼠模型,链球菌细胞壁诱导的关节炎大鼠、小鼠模型和转基因小鼠模型与人RA发病机制和病理变化等有着相似特点,是研究RA、筛选抗炎免疫药物较理想的实验性病理模型。探讨RA动物模型的发病机制及其与临床的关系,对进一步了解RA病理、生理、免疫等特点及寻找安全有效的治疗RA的药物十分重要。该文将对几种常用的实验性关节炎模型的建立、造模特点、发病机制、与RA的异同等方面进行综述。     

类风湿性关节炎实验动物模型的研究进展

目的综合国内外关于类风湿性关节炎(RA)的研究报道,分析总结出一种较为理想的实验动物模型,为后期相关的药效学研究奠定基础。方法通过查阅万方、维普、中国知网以及外文数据库等,了解国内外关于RA动物模型的研究现状。结果由于RA的发病原因及机制仍不明确,目前没有哪种动物模型能全面地反映该病的发病特征,有待进一步研究。结论胶原诱导的关节炎和佐剂性关节炎是目前实验室常用的2种研究RA的动物模型,其他动物模型可以针对具体病变部位而选择,选择具有局限性但也有一定的特异性,具有潜在的研究价值。     

类风湿关节炎动物模型的研究进展

<正>类风湿关节炎(RA)的动物模型有多种,本文将对几种较典型的关节炎模型的制备方法、造模特点、发病机制等方面进行比较研究,以选择更为理想的动物模型。     

Ⅱ型胶原诱导的小鼠关节炎动物模型的建立及影响因素

类风湿性关节炎(RA)是一种顽固性、致畸性自身免疫性疾病。Ⅱ型胶原诱导的小鼠关节炎(CIA)表现为严重的多关节性炎,并能引起慢性、破坏性关节损伤,与RA有很多相似之处,目前国际上广泛用于RA发病机制的研究以及创新药物的研发。该文就CIA实验动物模型的建立以及CIA发生病变的主要影响因素进行综述。     

佐剂性关节炎大鼠细胞免疫功能的变化

类风湿性关节炎(Rheumatoid Arthritis,RA)是一类严重危害人类身体健康的常见自身免疫性疾病.佐剂性关节炎(Adjuvant Arthritis, AA)大鼠是研究类风湿性关节炎(RA)及评价防治RA药物的常用动物模型之一,其病理表现与RA有一定的相似之处,如病变关节肿胀,细胞免疫功能异常等[1],但其免疫病理特征及发病机制目前仍不十分清楚.本实验研究了佐剂性关节炎大鼠的细胞免疫功能变化,探讨细胞免疫功能在大鼠佐剂性关节炎发病机制中的作用.     

2型糖尿病小鼠模型的研究进展

2型糖尿病是一种受遗传因素和环境因素共同影响的疾病,动物模型在糖尿病及其并发症的发病机制、预防和治疗方法的研究中发挥重要作用,当前应用广泛的糖尿病小鼠模型主要有自发性糖尿病小鼠模型、实验性糖尿病小鼠模型和基因工程糖尿病小鼠模型。不同实验方法制备的糖尿病小鼠具有模拟临床糖尿病不同方面的特点,该文对各个模型的发病机制和生理特点等方面进行了阐述,以利于研究者根据各自不同的实验需求和目的选择合适的糖尿病小鼠模型来验证或实现科研设想。     

偏头痛动物模型研究现状

从偏头痛动物模型的造模机制、造模方法、观察指标以及模型特点4个方面,综述了近年来国内外常用、经典的偏头痛动物模型,以期为今后偏头痛基础研究或药物的开发提供一定的实验指导.     

化学诱导型结肠炎动物模型的研究进展

实验动物模型对于发现抗炎症性肠病的药物及探讨其发病机制具有重要作用。通过文献查阅,综述了目前用于炎症性肠病药理学研究的化学诱导型结肠炎动物模型的研究进展,从制备方法、模型特征、可能的致病机制和用途等方面进行了详细的论述。对于认知和了解炎症性肠病的发病机制及在实验中对IBD实验动物模型的选择提供一定的依据。     

New drug discovery strategies for rheumatoid arthritis: a niche for nonhuman primate models to address systemic complications in inflammatory arthritis

INTRODUCTION: Despite the tremendous advances made in the treatment of rheumatoid arthritis (RA), there is still excess mortality observed in RA patients, which is mainly caused by cardiovascular disease (CVD). Altered lipid metabolism plays a major role in the etiology of CVD. A second common complication observed in RA patients is anemia. Both conditions are serious, reduce quality of life and are undertreated. AREAS COVERED: The authors postulate that there is a specific niche for nonhuman primate models of inflammatory arthritis to address these systemic complications that occur in RA. Furthermore, the authors postulate that these nonhuman primate models are a useful platform to unveil the mechanisms underlying dyslipidemia and anemia, which are responsible for the manifestation of these complications. EXPERT OPINION: The presence of currently untreated systemic complications of RA, such as dyslipidemia and anemia, provides interesting opportunities to include these in the preclinical evaluation of new therapies. In the selection of relevant models for the evaluation of new treatments for RA or the identification of new targets for therapy, we postulate that nonhuman primates should be considered as a valid preclinical model. Because of their closer immunological and physiological proximity to humans, these models in nonhuman primates can be valuable for studying disease-related aspects that cannot be addressed in rodent models.     

New drug discovery strategies for rheumatoid arthritis: a niche for nonhuman primate models to address systemic complications in inflammatory arthritis

Introduction: Despite the tremendous advances made in the treatment of rheumatoid arthritis (RA), there is still excess mortality observed in RA patients, which is mainly caused by cardiovascular disease (CVD). Altered lipid metabolism plays a major role in the etiology of CVD. A second common complication observed in RA patients is anemia. Both conditions are serious, reduce quality of life and are undertreated.

Areas covered: The authors postulate that there is a specific niche for nonhuman primate models of inflammatory arthritis to address these systemic complications that occur in RA. Furthermore, the authors postulate that these nonhuman primate models are a useful platform to unveil the mechanisms underlying dyslipidemia and anemia, which are responsible for the manifestation of these complications.

Expert opinion: The presence of currently untreated systemic complications of RA, such as dyslipidemia and anemia, provides interesting opportunities to include these in the preclinical evaluation of new therapies. In the selection of relevant models for the evaluation of new treatments for RA or the identification of new targets for therapy, we postulate that nonhuman primates should be considered as a valid preclinical model. Because of their closer immunological and physiological proximity to humans, these models in nonhuman primates can be valuable for studying disease-related aspects that cannot be addressed in rodent models.     

The therapeutic potential of costimulatory blockade with CTLA4Ig in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterised by joint inflammation and destruction. Controversy exists regarding the significance and exact role of activated T cells in RA. CTLA4Ig is a soluble fusion protein (cytotoxic T lymphocyte-associated antigen 4 fused to the heavy chain constant region of human IgG1), which represents the first in a new class of agents called costimulation blockers. By blocking the second signal required for optimal T-cell activation, CTLA4Ig has demonstrated efficacy in a variety of spontaneous and induced animal models of autoimmunity. A Phase II clinical study in RA showed CTLA4Ig was efficacious with an acceptable safety profile. These results suggest that activated T cells may be important in RA pathogenesis and that costimulation blockade may be a novel therapeutic approach for this disorder.     

Preclinical models of arthritic disease in non-human primates

The costs for the development of new drugs have increased dramatically over the past 30 years. One of the main reasons for this increase is the low success rate of new drugs being approved for patient use, which is, in part, a consequence of the common use of rodent models for preclinical validation of efficacy. Especially in the development of biologicals, which are now successfully used in the treatment of rheumatoid arthritis, the selection of the right animal model is pivotal. Non-human primates could help to bridge the evolutionary gap between rodent models and human patients.     

IL-33: a promising therapeutic target for rheumatoid arthritis?

Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA). Recently, the IL-1-family-related cytokine, IL-33, was detected at high levels in experimental inflammatory arthritis and in the early phase of human RA, and was reported to exert profound pro-inflammatory effects in several experimental autoimmune models. Moreover, administration of IL-33 leads to the development of severe inflammatory arthritis, suggesting that IL-33 may be therapeutically relevant in RA, and the targeting of IL-33 or the IL-33 receptor has been proposed as a potential therapeutic approach for autoimmune diseases such as RA. In this article, we discuss the biological features of IL-33 and summarize recent advances in our understanding of the role of IL-33 in the pathogenesis and treatment of RA. It is hoped that this information may aid the development of novel therapeutic strategies for RA.     

Mast cells as a target of rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a chronic inflammatory disease and its exact cause and pathophysiological process remain unclear. Fibroblast-like synoviocytes, macrophages and T lymphocytes are considered to be the major contributors in the pathophysiological process of RA; however, an increasing number of papers have drawn attention to the potential role of mast cells (MCs) in the process. In an animal model of RA, we reported an increase in MC numbers in the arthritic region, which agreed with the observation in human RA. In addition, a good correlation between the number of MCs and the development of disease was observed. However, there has been little experimental or clinical evidence of the beneficial effects of the modification of MC activity on the pathogenesis of RA and this is the weak point of the hypothesis. We therefore studied the effects of a MC-stabilizing compound, cromoglicate lisetil (CL), which is an orally deliverable prodrug of cromolyn sodium, on the RA disease model. The MC-stabilizer had efficacy in a mouse model. The beneficial effects of CL in this animal model further suggested the contribution of MCs in the pathophysiological process of RA. Concerning the contributive mechanism of MC on the pathogenesis of RA, our results using a disease model suggested that activation of MC chymase and matrix metalloproteinases might be involved. MC is now considered to be one of the targets of RA treatment.     

Genetic rodent models of depression

Are there appropriate rodent models for human depressive disorders? A model that targets a core aspect of depression can become a helpful tool in the analysis of the causes, genetic or environmental, that result in symptoms homologous to those of depressed patients. Rodent models can also allow the study of the pathophysiology of specific behaviors, and can help in predicting therapeutic responses to pharmacological agents. A rodent model of depression should satisfy as many of the three main criteria as possible: similar etiology, similar pathophysiology, and similar treatment to the human condition. A wide range of rodent models of depression has been developed so far, including genetic models.     

Nongenotoxic carcinogens in the regulatory environment

The biological activity of many carcinogens is to directly induce mutational events, thereby altering the information encoded in the DNA. Short-term tests for potential carcinogens and risk assessment models generally rely on the assumption that the agent in question will operate through a genotoxic mechanism. However, carcinogenesis is a multistep process, and it is increasingly clear that the primary biological effect for many carcinogenic chemicals involves events other than direct DNA reactivity. For many experimental rodent models as well as human cancers, nongenotoxic mechanisms appear to be the driving force in the formation of tumors. Many of these nongenotoxic mechanisms are highly species-specific. Thus, it is increasingly important to ask if the rodent model applies to the human situation at all, in addition to the examination of appropriate, hypothetical, mathematical risk assessment models. More research is now being focused to better define the mechanisms by which the many distinctly different classes of nongenotoxic carcinogens are acting. This understanding will become the basis for new predictive assays and more realistic risk assessment models. If specific conditions are met, then a no observed effect level with a safety factor may be the most appropriate risk model for some carcinogens.