Rogai V, Lories R J, Guiducci S, Luyten F P, Matucci Cerinic M
Department of Biomedicine, Division of Rheumatology, University of Florence, AOUC, Florence, Italy.
Clin Exp Rheumatol. 2008 Sep-Oct;26(5):941-6.
Systemic sclerosis (SSc) is a complex systemic disease. It is characterised by fibrosis, of the skin and internal organs, as lungs, kidney, heart and gastrointestinal tract. As the aetiology of SSc is unknown, numerous animal models have been developed to better understand the pathogenesis of the disease and to test potentially useful therapeutic interventions. Although several animal models have been described, predominantly in mice, none reproduces precisely all manifestations of SSc. However, all animal models display tissue fibrotic changes similar to those present in SSc. This review is focused on the principal animal models and the molecular pathways involved. Animal models can be divided into two groups. In one group the pathologic phenotype is the result of a genetic mutation ( tight skin 1 and tight skin 2,UCD 200). In the second group, the pathologic alterations are induced in normal animals by manipulation of their immune system (sclerodermatous graft-vs-host disease (Scl GVHD) induced by transplantation, or by administration of exogenous substances). In the future, the development of additional animal models may become important in the further understanding of the alteration of the molecular pathways that regulate a physiologic processes to induce tissue fibrosis, the hallmark of this disease, and to identify and test targeted therapeutic agents.
系统性硬化症（SSc）是一种复杂的全身性疾病。其特征是皮肤和内部器官（如肺、肾、心脏和胃肠道）出现纤维化。由于SSc的病因不明，人们已开发出多种动物模型，以更好地了解该疾病的发病机制，并测试可能有用的治疗干预措施。尽管已经描述了几种动物模型，主要是在小鼠中，但没有一种能精确再现SSc的所有表现。然而，所有动物模型都显示出与SSc中存在的类似的组织纤维化变化。本综述聚焦于主要的动物模型及相关分子途径。动物模型可分为两组。一组中，病理表型是基因突变的结果（紧皮1和紧皮2，UCD 200）。在第二组中，通过操纵正常动物的免疫系统（移植诱导的硬皮病移植物抗宿主病（Scl GVHD）或给予外源性物质）诱导病理改变。未来，开发更多动物模型对于进一步理解调节生理过程以诱导组织纤维化（该疾病的标志）的分子途径的改变，以及识别和测试靶向治疗药物可能变得至关重要。
