Preconditioning protects ischemic rabbit heart by protein kinase C activation.
Preconditioning protects ischemic rabbit heart by protein kinase C activation.
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DOI：
10.1152/ajpheart.1994.266.3.h1145
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发表时间：
1994-03
期刊：
影响因子：
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通讯作者：
K. Ytrehus;Yongge Liu;J. Downey
中科院分区：
文献类型：
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作者：
K. Ytrehus;Yongge Liu;J. Downey
缺血预适应对兔心肌的保护作用被认为与腺苷受体有关，但保护作用的信号通路尚未确定。这项研究测试了蛋白激酶C是否可能参与其中。分别给予星形孢子素(50微克/kg)或多粘菌素B(24 mg/kg)两种蛋白激酶C抑制剂，造成兔局部心肌缺血30min再灌流180min。一半的兔被预适应，而另一半作为非预适应的对照组。未经药物或经星形孢菌素或多粘菌素B治疗的未经预适应的心脏分别有37.8+/-3.1%、40.5+/-2.8%和42.0+/-7.0%的心肌梗死发生在危险区。预适应将脑梗塞面积限制在7.3+/-2.7%。这两种抑制剂分别阻断了36.2+/-2.7和40.9+/-2.5%的危险区域梗塞的预适应心脏的保护作用。用4β-佛波酯(PMA)或1-油基-2-乙酰甘油(OAG)激活蛋白激酶C可模拟缓冲液灌流心脏的预适应。PMA(0.01nmoL/min)或OAG(10nmoL/min)作用5min，然后冲洗10min。局部缺血30min后，PMA组和OAG组的脑梗塞面积有限(未治疗对照组分别为6.4+/-1.4和11.7+/-3.3比28.0+/-4.5%)，与缺血预适应相当(11.8+/-2.2%)。多粘菌素B还阻断了缺血预适应对离体心的保护作用(33.0+/-5.0%)。
Myocardial protection in the rabbit induced by ischemic preconditioning is thought to be adenosine receptor linked, but the signaling pathway responsible for the protection has yet to be identified. This study tests whether protein kinase C could be involved. Either of two inhibitors of protein kinase C, staurosporine (50 micrograms/kg) or polymyxin B (24 mg/kg), were administered to rabbits subjected to 30 min regional myocardial ischemia followed by 180 min reperfusion. Half of the rabbits were preconditioned while the other half served as nonpreconditioned controls. Nonpreconditioned hearts without drug or treated with staurosporine or polymyxin B resulted in 37.8 +/- 3.1, 40.5 +/- 2.8, and 42.0 +/- 7.0% infarction of the risk zone, respectively. Preconditioning limited infarct size to 7.3 +/- 2.7%. Both inhibitors blocked protection in preconditioned hearts with 36.2 +/- 2.7 and 40.9 +/- 2.5% of the risk zone infarcted, respectively. Activation of protein kinase C with 4 beta-phorbol 12-myristate 13-acetate (PMA) or with 1-oleyl-2-acetyl glycerol (OAG) mimicked preconditioning in buffer-perfused hearts. PMA (0.01 nmol/min) or OAG (10 nmol/min) for 5 min was followed by 10 min of washout. Infarct size after 30 min regional ischemia was limited in the PMA and OAG groups (6.4 +/- 1.4 and 11.7 +/- 3.3 vs. 28.0 +/- 4.5% in untreated controls) and was equipotent with ischemic preconditioning (11.8 +/- 2.2%). Polymyxin B also blocked protection from ischemic preconditioning in the isolated heart (33.0 +/- 5.0%).(ABSTRACT TRUNCATED AT 250 WORDS)