Qu W-M, Miyazaki T, Terada M, Okada K, Mori S, Kanno H, Nose M
Department of Pathology, Ehime University School of Medicine, Japan.
Clin Exp Immunol. 2002 Jul;129(1):27-34. doi: 10.1046/j.1365-2249.2002.01881.x.
In this study we established a new animal model for exploring the pathogenesis of autoimmune pancreatitis. We have found previously that MRL/Mp-+/+(MRL/+) mice develop pancreatitis spontaneously by an autoimmune mechanism but only when they are more than 34 weeks old. Because this disease might be a model of multi-factorial diseases controlled by genetic and environmental factors, beginning at 6 weeks old, we injected polyinosinic:polycytidylic acid (poly I:C) into MRL/+ mice and in addition, into MRL/Mp mice bearing the Fas deletion mutant gene, lpr (MRL/lpr). Poly I:C induced chronic severe pancreatitis in all the MRL/+ mice and to a lesser extent in the MRL/lpr mice by 18 weeks of age. There was no pancreatitis in control mice of both strains at the same age. Other than chronic pancreatitis, no severe autoimmune diseases were observed in MRL/+ mice. Immunohistochemical examinations revealed predominant infiltration of CD4+ T cells and Mac-2+ activated macrophages in the pancreatic lesions. Splenic expression of the mRNAs for TNF-alpha and IL-10, which is known to suppress the development of pancreatitis, were increased in both strains of mice. These findings suggest that an MRL strain of mice treated with poly I:C might be a good model for developing new approaches to the study of the pathogenesis of autoimmune pancreatitis.
在本研究中，我们建立了一种新的动物模型，用于探索自身免疫性胰腺炎的发病机制。我们之前发现，MRL/Mp-+/+(MRL/+)小鼠通过自身免疫机制自发发生胰腺炎，但仅在它们超过34周龄时才会出现。由于这种疾病可能是由遗传和环境因素控制的多因素疾病模型，从6周龄开始，我们将聚肌苷酸:聚胞苷酸（poly I:C）注射到MRL/+小鼠中，此外，还注射到携带Fas缺失突变基因lpr的MRL/Mp小鼠（MRL/lpr）中。到18周龄时，poly I:C在所有MRL/+小鼠中诱发了慢性重症胰腺炎，在MRL/lpr小鼠中诱发程度较轻。相同年龄的两种品系对照小鼠均未出现胰腺炎。除慢性胰腺炎外，MRL/+小鼠未观察到严重的自身免疫性疾病。免疫组织化学检查显示，胰腺病变中主要有CD4+ T细胞和Mac-2+活化巨噬细胞浸润。已知可抑制胰腺炎发展的TNF-α和IL-10的脾脏mRNA表达在两种品系小鼠中均增加。这些发现表明，用poly I:C处理的MRL品系小鼠可能是开发研究自身免疫性胰腺炎发病机制新方法的良好模型。
