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|本期目录/Table of Contents|

TNFα在心肌缺血/再灌注重塑期的保护作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第3期
页码:
357-360，365
栏目:
综述
出版日期:
2014-03-20

文章信息/Info

Title:
Cardioprotective effect of TNF-α during the remodeling period of myocardial ischemia/reperfusion
作者:
王艺璇; 余志斌
（第四军医大学航空航天生理学教研室，陕西 西安 710032）
Author(s):
WANG Yi xuan;  YU Zhi bin
(Department of Aerospace Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
肿瘤坏死因子α; 心肌; 缺血/再灌注损伤; 肿瘤坏死因子受体
Keywords:
tumor necrosis factor;  myocardial;  ischemia/reperfusion injury;  tumor necrosis factor receptor
分类号:
R392.12
DOI:
-
文献标识码:
A
摘要:
大量研究表明，肿瘤坏死因子α（TNFα）在心肌缺血/再灌注(I/R)损伤中，既能促进心肌损伤，又具有保护心肌的作用，这种看似相互矛盾的作用，系因在心肌I/R的不同时期由不同的信号转导通路所介导。在心肌I/R的急性期，缺血区冠脉血管床的内皮细胞受损，黏附血中巨噬细胞与淋巴细胞可释放大量可溶型TNFα(sTNFα)。高浓度的sTNFα可激活TNF的1型受体（TNFR1）及其下游信号转导通路，引起心肌细胞凋亡。在心肌I/R的重构期或修复期，虽然血中sTNFα的水平高于生理浓度，但血中可溶型TNFR的水平增加可中和sTNFα，阻止其对正常心肌组织的损害。心肌局部缺血可刺激心肌细胞与成纤维细胞合成TNFα，在细胞膜上装配为跨膜型TNFα，激活相邻细胞的2型TNF受体（TNFR2）及其下游信号转导通路，增强心肌细胞钙转运而增强其收缩功能，同时拯救缺血边界区可存活的心肌细胞。心肌局部跨膜型TNFα还能募集间充质干细胞，分泌多种细胞生长因子，改善心功能。TNFα可通过组蛋白去乙酰化酶1(HDAC1)调节核转录因子κB(NF-κB)的转录活性，保护心肌细胞在持续的TNFα作用下得以存活。跨膜型TNFα还可激活心肌中固有的干细胞向心肌细胞分化，修复受损的心肌组织。
Abstract:
Many studies have shown that tumor necrosis factor-α (TNF-α) plays a self-contradictory role in myocardial ischemia/reperfusion (I/R) injury, i.e., protection and injury. The self-contradictory effect actually takes place in different periods of myocardial I/R mediated by the different signal transduction pathways. Acute I/R damages coronary endothelia in ischemia zone and induces the adherence of macrophages and lymphocytes to release soluble TNFα (sTNFα). High levels of sTNF-α activate tumor necrosis factor receptor 1 (TNFR1) and its downstream signal transduction pathways to cause cardiomyocyte apoptosis. In the remodeling or repairing period of myocardial I/R, althought sTNF-α level is higher than that of physiological condition in plasma, the increased soluble TNFR neutralizes sTNF-α to prevent it from injuring normal myocardial tissue in the remote zone. The local ischemia of myocardium stimulates cardiomyocytes and fibroblasts to synthesize transmembrane TNF-α, which then activates tumor necrosis factor receptor 2 and its downstream transduction pathway in nearby cells. Therefore, calcium transport and contractile function of cardiomyocytes enhanced and survived cardiomyocytes in the border zone are saved. The local transmembrane TNF-α can recruit mesenchymal stem cells to release cytokine and growth factors, which improve cardiac function. Transmembrane TNF-α depresses histone deacetylases 1 (HDAC1). HDAC1 provides a molecular switch for determining cellular survival in the TNF-α pathway via modulating NF-κB gene transcription. Transmembrane TNFα also results in resident cardiac stem cells differentiated toward cardiomyocytes and repair the injured myocardium tissue.

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备注/Memo

备注/Memo:
收稿日期：2013-11-21.
通讯作者：余志斌，教授，主要从事应用心血管生理学研究 Email：yuzhib@fmmu.edu.cn
作者简介：王艺璇，本科生 Email：345354650@qq.com
更新日期/Last Update: 2014-03-21