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Pathobiochemical and immunological study on infection-accelerated atherosclerosis and its regulation.

感染加速动脉粥样硬化及其调控的病理生化和免疫学研究。

基本信息

批准号：
18590296
负责人：
MATSUURA Eiji
金额：
$ 2.53万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

In the present study, we studied precise mechanisms on the Helicobacter pylori (H pylori Infection)- infection develops atherosclerosis in atherosclerosis-prone model (apoe^<-/-> ldlr^<+/->) mice. Actually, (1) we calculated stricture grade of stethartery and analyzed activation of endothelial cells, foam cell formation of macrophages, expression of scavenger receptors, infiltration of β2-glycoprorein (β2GPI) I into the intima, production of adhesion molecules and cytokines. (2) As well as general blood parameters of lipid metabolism, oxidized LDL/β2GPI complexes and anti-Hp-HSP60 antibodies, Thl and Th2 dependent cytokines as immunologic markers in plasma and/or in supernatant of culture with splenocytes were also assayed (3) Further, surface markers of cultured splenocytes were detected by flow-cytometry. In clinical study with H pylori-positive hypertensive patients, we pathobiochemically, immunologically, and clinical immunologically analyzed whether infection, especially with H pylori and humeral immunity against Hp-HSP60 were involved in development of atherosclerosis. In results: the oral infection with H. pylori induced Thl immune response against Hp-HSP60 and resulted in developing atherosclerosis. Further, the cellular immunity-mediated atherosclerosis was significantly reduced by immunization with Hp-HSP60 together with adjuvant Plasma levels of novel marker of atherosclerosis, i.e., oxidized LDL/β2GPI complexes, which we have recently observed were associated with the development of atherosclerosis. Thus, it was shown a possibility that immune response to chronic infection accelerates atherosclerosis and vaccination prevents the development We got the ethical approval and establish the condition for the clinical study. We observed significant association between the development of cardiovascular dive and appearance of anti-Hp-HSP60 antibodies and successfully cloned a T cell specific to Hp-HSP60 in the human study.

在本研究中，我们研究了幽门螺杆菌（Hpylori Infection）感染在动脉粥样硬化易感模型（apoe^<-/-> ldlr^<+/->）小鼠中发展动脉粥样硬化的确切机制。（1）计算狭窄程度，分析内皮细胞活化、巨噬细胞泡沫细胞形成、清道夫受体表达、β2-糖蛋白I（β 2-glycoprorein，β2GPI）I向内膜的浸润、粘附分子和细胞因子的产生。(2)除测定一般血脂代谢指标外，还检测了血浆和/或脾细胞培养上清中氧化型LDL/β2GPI复合物、抗Hp-HSP 60抗体、Th 1和Th 2依赖性细胞因子等免疫学指标。（3）流式细胞术检测脾细胞表面标志物。本研究以H pylori阳性的高血压患者为研究对象，从病理生物化学、免疫学和临床免疫学角度分析了H pylori感染，特别是H pylori感染和Hp-HSP 60的体液免疫是否参与了动脉粥样硬化的发生。结果表明：口腔感染H. pylori诱导Th 1型细胞产生抗Hp-HSP 60的免疫应答，导致动脉粥样硬化的发生。此外，细胞免疫介导的动脉粥样硬化通过用Hp-HSP 60与佐剂一起免疫而显著降低。动脉粥样硬化的新标记物，即，氧化型LDL/β2GPI复合物与动脉粥样硬化的发生发展有关。因此，它显示了一种可能性，即对慢性感染的免疫反应加速动脉粥样硬化，疫苗接种阻止了发展。我们获得了伦理批准，并为临床研究创造了条件。我们观察到心血管疾病的发展与抗Hp-HSP 60抗体的出现之间存在显著的相关性，并在人体研究中成功克隆了Hp-HSP 60特异性T细胞。