A Study on the Role of Protease Produced by Vibrio cholerae non-01 in the Pathogenic Mechanism of Sepsis.

关于霍乱弧菌感染的病例报道很多，可能会蔓延到肠道外器官。它可导致败血症和多器官衰竭，特别是在免疫功能低下的宿主。霍乱弧菌产生的一种金属蛋白酶可能参与了霍乱弧菌侵袭组织或血管的机制。因为它是激活激动素级联通路的通透性因子，也是炎症病变中白细胞迁移产生的基质金属蛋白酶的激活因子。我们当时正试图建立霍乱弧菌019引起的脓毒症动物模型，以阐明霍乱弧菌的入侵机制。通过对金属蛋白酶在霍乱弧菌致病机制和败血症模型组织病理学研究中的作用的研究，得到以下结果：(1)改进了霍乱酶的纯化方法；(2)建立了用ECL试剂盒免疫印迹检测霍乱酶的检测体系；(3)分析了霍乱毒素的酶切位点；(4)建立了霍乱弧菌019小鼠败血症模型；(5)霍乱酶参与了败血症的发病机制；(6)iNOS参与了败血症的发病机制。

There are many reports on the cases of Vibrio cholerae infection which may extend to extra-intestinal organs. It can result in sepsis and multiple organ failure especially in immunocompromised hosts. It is then considered that a metalloprotease produced by Vibrio cholerae may be involved in its invasive mechanisms of vibrios into tissues or vessels. Because it is a permeability factor to activate kinin cascade and an activating factor of a matrix metalloprotease produced by leukocytes migrating in the inflammatory lesion. We were then trying to develop an animal model of sepsis due to Vibrio cholerae 019 to elucidate the invasive mechanisms of Vibrio cholerae. The results obtained through the study on the role of metalloprotease in pathogenic mechanisms of Vibrio cholerae and histopathological findings in sepsis model are as follows ;(1)Improvement of purification method of choleraprotease.(2)Establishment of assay system of choleraprotease using immunoblotting with ECL kit.(3)Analysis of nicking site of cholera toxin by choleraprotease.(4)Development of mouse sepsis model using Vibrio cholerae 019.(5)Involvement of choleraprotease in the pathogenic mechanism of sepsis.(6)Involvement of iNOS in the pathogenic mechanism of sepsis.