Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning
Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning
复制标题
DOI：
10.1006/jmcc.2001.1338
复制
发表时间：
2001-04-01
影响因子：
5
通讯作者：
Auchampach, JA
中科院分区：
文献类型：
--
作者：
Guo, Y;Bolli, R;Auchampach, JA
我们使用A(3)腺苷受体（AR）基因遗传破坏的小鼠(A（3)AR（-/-）小鼠）来评估A(3)AR在调节心肌缺血/再灌注损伤和预适应（PC）中的体内作用。令人惊讶的是，与野生型小鼠(A(3)AR（+/+）相比，冠状动脉闭塞30分钟和再灌注24小时后，A(3)AR（-/-）的梗死面积减少了35%，梗死面积的减少不是心率、体温差异或心脏A(1)AR表达增加的结果。然而，A(3)AR（-/-）小鼠梗死区域内的中性粒细胞浸润较少。此外，在a (3)AR（-/-）和a (3)AR（+/+）小鼠中，单次（1次5分钟闭塞）或多次（6次4分钟闭塞）缺血诱导的缺血性PC均产生了相当的梗死面积减少。这些结果表明，在小鼠中，(i) A(3) ar在急性心肌缺血/再灌注损伤中发挥损伤作用，可能通过加剧炎症反应，以及（ii） A(3) ar在缺血性PC早期的发展中不是必需的。(C) 2001学术出版社。
We used mice with genetic disruption of the A(3) adenosine receptor (AR) gene (A(3)AR(-/-) mice) to assess the in vivo role of the A(3)AR in modulating myocardial ischemia/reperfusion injury and preconditioning (PC). Surprisingly, infarct size induced by 30 min of coronary artery occlusion and 24 h of reperfusion was 35% smaller in A(3)AR(-/-) compared to wild-type mice (A(3)AR(+/+)), The reduction in infarct size was not the result of differences in heart rate, body temperature or increased cardiac expression of A(1)ARs. However, neutrophil infiltration within infarcted regions was less in A(3)AR(-/-) mice. Furthermore, ischemic PC induced by either a single episode (one 5 min occlusion) or multiple episodes (six 4 min occlusions) of ischemia produced equivalent reductions in infarct size in A(3)AR(-/-) and A(3)AR(+/+) mice. These results indicate that, in the mouse, (i) A(3)ARs play an injurious role during acute myocardial ischemia/reperfusion injury, possibly by exacerbating the inflammatory response, and (ii) A(3)ARs are not necessary for the development of the early phase of ischemic PC. (C) 2001 Academic Press.