Gysembergh A, Margonari H, Loufoua J, Ovize A, André-Fouët X, Minaire Y, Ovize M
Laboratoire de Physiologie Lyon-Nord, University Claude Bernard, France.
Am J Physiol. 1998 Mar;274(3):H955-64. doi: 10.1152/ajpheart.1998.274.3.H955.
We sought to determine whether stretch-induced preconditioning may be related to activation of adenosine receptors, ATP-sensitive K+ (K+ATP) channels, and/or protein kinase C (PKC) in the rabbit heart. Anesthetized rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Ischemic preconditioning was induced by one episode of 5 min of ischemia followed by 5 min of reperfusion, and stretch preconditioning was induced by a transient volume overload. The abilities of gadolinium (Gd3+), a blocker of stretch-activated channels, glibenclamide (Glib), a blocker of K+ATP channels, 8-(p-sulfophenyl)-theophylline (8-SPT), a blocker of adenosine receptors, and polymyxin B (PMXB), an antagonist of PKC, to prevent the infarct size-limiting effect of stretch-induced preconditioning were evaluated. Because the infarct size-reducing effect of stretch occurred in the absence of ischemia and was prevented by previous administration of Gd3+, Glib, 8-SPT, and PMXB, we propose that activation of mechanosensitive ion channels protects the rabbit heart from subsequent sustained ischemic insult, likely through a mechanism that involves downstream activation of PKC, adenosine receptors, and/or K+ATP channels.
我们试图确定拉伸诱导的预处理是否可能与兔心脏中腺苷受体、ATP敏感性钾离子(K⁺ATP)通道和/或蛋白激酶C(PKC)的激活有关。将麻醉的兔子进行30分钟的冠状动脉闭塞,随后再灌注3小时。缺血预处理通过5分钟的缺血发作后再灌注5分钟诱导,拉伸预处理通过短暂的容量超负荷诱导。评估了拉伸激活通道阻滞剂钆(Gd³⁺)、K⁺ATP通道阻滞剂格列本脲(Glib)、腺苷受体阻滞剂8-(对磺基苯基)茶碱(8-SPT)和PKC拮抗剂多粘菌素B(PMXB)预防拉伸诱导的预处理的梗死面积限制作用的能力。由于拉伸的梗死面积减小作用在无缺血的情况下发生,并且被先前给予的Gd³⁺、Glib、8-SPT和PMXB所阻止,我们提出机械敏感离子通道的激活保护兔心脏免受随后的持续缺血损伤,可能是通过一种涉及PKC、腺苷受体和/或K⁺ATP通道下游激活的机制。