FOR NEW METHOD TO MAKE A DIAGNOSIS OF AUTOIMMUNE CARDIOMYOPATHY

诊断自身免疫性心肌病的新方法

基本信息

批准号：
16590713
负责人：
IZUMI Tohru
金额：
$ 2.3万
依托单位：
KITASATO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590713/
关键词：
DILATED CARDIOMYOPATHY AUTOIMMUNE Gi PROTEIN SIGNAL ERYTHROPOIETIN T CELL G蛋白シグナル阻害 β遮断薬

项目摘要

The G protein through β-adrenergic receptors has been focused on as a modulator of not only myocardial contractility but also immune response. Thus, firstly, the immunomodulatory effects of the inhibitory G (Gi) protein on myocardial inflammation are studied. Myosin-immunized Lewis rats (EAM : experimental autoimmune myocarditis/cardiomyopathy) were divided into two groups : administered with pertussis toxin (PTX), a representative Gi protein inhibitor, simultaneously with immunization (in induction phase) and the other administered after immunization (in effector phase). They were evaluated adjunctive effect of PTX on EAM. With the use in induction phase, PTX deteriorated EAM. On the other hand, in the use in effector phase, PTX improved its disease severity. This bidirectional G protein signal must be one of the major immunomodulating pathways in autoimmune cardiomyopathy.On the other hand, erythropoietin (EPO) has a protective effect on myocardial damage. Thus, secondly, immunomodulatory effects of EPO on myocardial inflammation were investigated. EAM rats were treated daily with either EPO. EPO markedly reduced severity in EAM with the reduction of IFN-gamma/troponin T and IL-10/TNTmRNA in the myocardium. Although EPO did not suppress the proliferation of myosin-specific, myocarditogenic T cells in vitro, EAM produced by intravenous transfer of those T cells were ameliorated by daily administration of EPO. EPO has anti-inflammatory effect on the effecter phase.For establishment of new method to make a diagnosis of autoimmune myocarditis in human being, the above mentioned two points are taken into account : Gi protein signal as beta-stimulation and erythropoietin as an intrinsic humoral factor.

通过β-肾上腺肾上腺素受体的G蛋白不仅是心肌收缩性，而且是免疫响应的调节剂。首先，抑制性G（GI）蛋白对心肌感染的免疫调节作用是研究的。将肌球蛋白免疫的路易斯大鼠（EAM：实验性自身免疫性心肌炎/心肌病）分为两组：用震颤毒素（PTX）施用，gi蛋白（PTX）是一种代表性的gi蛋白抑制剂，同时及其诱导阶段（在诱导阶段）和其他后期施加了效率（在诱导阶段）（在诱导阶段）（效应）。评估了PTX对EAM的辅助作用。随着注射阶段的使用，PTX确定了EAM。另一方面，在效应阶段的使用中，PTX改善了其疾病的严重程度。该双向G蛋白信号必须是自身免疫性心肌病的主要免疫调节途径之一。另一方面，促红细胞生成素（EPO）对心肌损伤具有保护作用。其次，研究了EPO对心肌感染的免疫调节作用。每天用任何EPO治疗EAM大鼠。 EPO显着降低了EAM的严重程度，随着心肌中IFN-GAMMA/Troponin T和IL-10/TNTMRNA的降低。尽管EPO并未抑制体外肌球蛋白特异性，心肌生成T细胞的增殖，但通过每天的EPO给药来改善这些T细胞静脉转移产生的EAM。 EPO对效应子阶段具有抗炎作用。建立新方法来诊断人类的自身免疫性心肌炎，上述两点被考虑在内：GI蛋白信号作为β蛋白质信号作为β刺激和红细胞生成素作为固有的体液因子。