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Elucidation of pathophysiology for various digestive diseases

阐明各种消化系统疾病的病理生理学

基本信息

批准号：
15209024
负责人：
CHIBA Tsutomu
金额：
$ 25.63万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

In this study, we tried to elucidate pathophysiology of H.pylori-induced gastyritis, autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) all of which involve immunological responses, and the following results were obtained. (1)In human, patients with gastric ulcer had Th1-predominant immunological response, whereas patients with duodenal ulcer were more polarized to Th2 response. Moreover, in patients with MALT lymphoma, Th2 reaction was remarkable. (2)In mice, severe gastritis developed by HP infection in C57black mice, a typical Th1-type strain, whereas no gastritis could be observed in Balb/c mice, a typical Th2-type strain. On the other hand, by thymectomy, severe gastritis seen in C57black mice disappeared and MALT lymphoma developed in Balb/c mice. Moreover, for MALT lymphoma B cell growth in vitro, in addition to HP presence of HP specific T cells and peripheral blood DC were essential. (3)By using serum of the patient who was negative for anti CAII antibody or anti-lactoferin but with high serum IgG titer, we identified pancreatic trypsin inhibitor as a candidate target for autoantibody in patients with autoimmune pancreatitis. (4)In patients with IBD, serum titiers for anti-Mycobacterium antibody was significantly higher than normal subjects, and involvement of Mycobacterium paratuberculosis infection in pathophysiology of human IBD was suggested. (5)Moreover, involvement of CMV as well as EBV infection in the pathophysiology of IBD was also suggested, and importance of measurement of and comparison of copy numbers of CMV gene in both affected and non-affected colonic site for diagnosis of CMV infection in patients with IBD was indicated. (6)For development of IBD, abnormality of permeability of epithelial barrier and that of regeneration of the epithelium were found to be involved. Accordingly, administration of growth factors such as bFGF, that enhances repair of epithelial cells appeared to be effective for the treatment of IBD.

本研究试图阐明幽门螺杆菌引起的胃炎、自身免疫性胰腺炎（AIP）和炎症性肠病（IBD）的病理生理学，所有这些都涉及免疫反应，并获得以下结果。(1)In在人类中，胃溃疡患者具有Th 1优势免疫应答，而十二指肠溃疡患者更偏向于Th 2应答。MALT淋巴瘤患者Th 2反应明显。(2)In C57 black小鼠（典型的Th 1型）感染HP后出现严重胃炎，而Balb/c小鼠（典型的Th 2型）未出现胃炎。另一方面，通过胸腺切除术，C57黑小鼠中观察到的严重胃炎消失，Balb/c小鼠中发生MALT淋巴瘤。此外，对于MALT淋巴瘤B细胞的体外生长，除了HP之外，HP特异性T细胞和外周血DC的存在是必需的。(3)By使用抗CAII抗体或抗乳铁蛋白阴性但具有高血清IgG滴度的患者的血清，我们将胰蛋白酶抑制剂鉴定为自身免疫性胰腺炎患者中自身抗体的候选靶标。(4)In IBD患者血清抗分枝杆菌抗体滴度明显高于正常人，提示副结核分枝杆菌感染参与了IBD的病理生理过程。（5）提示CMV和EBV感染均参与IBD的病理生理过程，并指出测定和比较IBD患者患侧和非患侧结肠CMV基因拷贝数对诊断CMV感染的重要性。（6）IBD的发生与上皮屏障通透性异常和上皮再生异常有关。因此，施用增强上皮细胞修复的生长因子如bFGF似乎对IBD的治疗有效。