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Expression and Role of Inflammatory Cytokines in Acute Myocardial Infarction -usingTNF, IL-1, Il-6 knock out mice-

炎症细胞因子在急性心肌梗塞中的表达和作用 -使用 TNF、IL-1、IL-6 敲除小鼠 -

基本信息

批准号：
13670742
负责人：
SUZUKI Hiroshi
金额：
$ 0.96万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670742/
关键词：
TNF-α IL-1β IL-6 Myocardial infarction Knock out mouse Cytokine

项目摘要

1. Acute myocardial infarction model was made by ligation of left anterior descending coronary arteries of TNF-α knock out mice (KO) and wild type (WT) mice. At 1, 3 and 7 days after infarction, cardiac ultrasound was performed, and the heart was excised for histological. immunohistochemical and morphological analysis.2. Tissue levels of TNF-α and IL-6were increased in infarcted and non-infarcted areas in WT at 1 day after infarction and increased more at 3 days.3. In ultrasound study, end-diastolic diameter was smaller in KO than in WT, and fractional shortening was higher in KO than WT at 3 and 7 days after infarction. Infiltration of inflammatory cells was observed from 1 day, and infiltration of macrophages were prominent at 3 days in histological examination, those of which were less in KO than WT in any period. Myocardial necrosis was prominent at 3 days, and wall thinning and left ventricular enlargement were observed at 7 days. In immnunohistochemical analysis, expression of metalloproteinase 2, 9, 13 was observed in infiltrating cells and cardiomyocytes in infracted and peri-infarcted areas at 1 day and prominent at 3 and 7 days. Those expressions were less in KO than in WT in any period. Furthermore, TUNEL positive cells representing apoptotic cells were less in KO than in WT in peri-infarcted area.4. In KO mice, the degree of myocardial damage was less marked, and the expression of metalloproteinase was smaller than in WT, suggesting the involvement of TNF-α in the pathogenesis after myocardial infarction partly through metalloproteinase. The expression of metalloproteinase in non-infarcted area indicates the involvement of metalloproteinase in the cardiac remodeling. Anti-cylokine therapy on cardiac failure and remodeling may became a useful strategy.

1. 采用结扎TNF-α敲除小鼠（KO）和野生型小鼠（WT）左冠状动脉前降支的方法制备急性心肌梗死模型。分别于梗死后1、3、7天行心脏超声检查，并切除心脏进行组织学检查。免疫组化及形态学分析在梗死后1天，WT梗死区和非梗死区TNF-α和il -6的组织水平均升高，在梗死后3天进一步升高。超声检查发现，梗死后3天和7天，KO患者的舒张末期内径小于WT患者，KO患者的分数缩短高于WT患者。第1天开始观察炎性细胞浸润，第3天组织学检查巨噬细胞浸润明显，KO组各时期均少于WT组。第3天心肌坏死明显，第7天心肌壁变薄，左心室增大。免疫组化分析显示，金属蛋白酶2、9、13在梗死区和梗死周围浸润细胞和心肌细胞中表达，在第1天，在第3天和第7天显著表达。在任何时期，这些表达在KO组均少于WT组。此外，在梗死周围区域，KO中TUNEL阳性细胞代表的凋亡细胞少于WT。与WT相比，KO小鼠心肌损伤程度较轻，金属蛋白酶表达较少，提示TNF-α部分通过金属蛋白酶参与心肌梗死后的发病机制。非梗死区金属蛋白酶的表达提示金属蛋白酶参与心脏重构。抗细胞因子治疗心力衰竭和重塑可能成为一种有用的策略。