Ischemic preconditioning in rats:: role of mitochondrial KATP channel in preservation of mitochondrial function
Ischemic preconditioning in rats:: role of mitochondrial KATP channel in preservation of mitochondrial function
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DOI：
10.1152/ajpheart.2000.278.1.h305
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发表时间：
2000-01-01
影响因子：
4.8
通讯作者：
Gross, GJ
中科院分区：
文献类型：
--
作者：
Fryer, RM;Eells, JT;Gross, GJ
我们研究了肌膜和线粒体K-ATP通道在大鼠缺血预适应(IPC)模型中的作用。梗死面积以危险区域的百分比(IS/AAR)表示。与对照组(56+/-1%)相比，IPC显著缩小了梗塞面积(7+/-1%)。IPC前给予肌膜K-ATP通道选择性拮抗剂HMR-1098并不显著减弱心肌保护作用。然而，IPC前5min给予线粒体K-ATP通道选择性拮抗剂5-羟基癸酸(5-HD)可部分取消心肌保护作用(40+/-1%)。静脉注射二氮嗪(10 mg/kg)也可降低IS/AAR(36.2+/-4.8%)，但这种作用可被5-HD消除。作为线粒体生物能功能的一个指标，检测AAR中的ATP合成率。未经处理的动物在2.12+/-0.30mmol.min(-1).mg线粒体蛋白(-1)的条件下合成了ATP。缺血再灌注大鼠以0.67+/-0.06pmol.min(-1)·mg线粒体蛋白(-1)合成ATP，IPC显著增加ATP合成至1.86+/-0.23mmol.min(-1)·mg线粒体蛋白-1。然而，在IPC前给予5-HD，对ATP合成的保护作用减弱(1.18+/-0.15mmol.min(-1).mg线粒体蛋白(-1))。这些数据与线粒体K-ATP通道的抑制通过减少IPC对线粒体功能的保护而减弱IPC的概念是一致的。
We examined the role of the sarcolemmal,and mitochondrial K-ATP channels in a rat model of ischemic preconditioning (IPC). Infarct size was expressed as a percentage of the area at risk (IS/AAR). IPC significantly reduced infarct size (7 +/- 1%) versus control (56 +/- 1%). The sarcolemmal K-ATP channel-selective antagonist HMR-1098 administered before IPC did not significantly attenuate cardioprotection. However, pretreatment with the mitochondrial K-ATP channel-selective antagonist 5-hydroxydecanoic acid (5-HD) 5 min before IPC partially abolished cardioprotection (40 +/- 1%). Diazoxide (10 mg/kg iv) also reduced IS/AAR (36.2 +/- 4.8%), but this effect was abolished by 5-HD. As an index of mitochondrial bioenergetic function, the rate of ATP synthesis in the AAR was examined. Untreated animals synthesized ATP at 2.12 +/- 0.30 mu mol.min(-1).mg mitochondrial protein(-1). Rats subjected to ischemia-reperfusion synthesized ATP at 0.67 +/- 0.06 pmol.min(-1).mg mitochondrial protein(-1); IPC significantly increased ATP synthesis to 1.86 +/- 0.23 mu mol.min(-1).mg mitochondrial protein-1. However, when 5-HD was administered before IPC, the preservation of ATP synthesis was attenuated (1.18 +/- 0.15 mu mol.min(-1).mg mitochondrial protein(-1)). These data are consistent with the notion that inhibition of mitochondrial K-ATP channels attenuates IPC by reducing IPC-induced protection of mitochondrial function.