High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels.
High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels.
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DOI：
10.1186/1475-2840-11-28
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发表时间：
2012-03-22
影响因子：
9.3
通讯作者：
Sumikawa K
中科院分区：
文献类型：
--
作者：
Ichinomiya T;Cho S;Higashijima U;Matsumoto S;Maekawa T;Sumikawa K
目前的研究旨在确定Rho激酶抑制剂盐酸法舒地尔（fasudil）在高血糖和正常血糖下是否具有心肌后处理（PostC）活性，如果有的话，该作用是否可以通过线粒体ATP敏感钾（m-KATP）通道介导。雄性斯普拉格-道利大鼠用戊巴比妥钠麻醉。打开胸腔后，所有大鼠均接受 30 分钟冠状动脉闭塞，然后再灌注 2 小时。大鼠在正常血糖或高血糖条件下再灌注前接受低剂量（0.15 mg/kg）或高剂量（0.5 mg/kg）法舒地尔或二氮嗪（一种 m-KATP 通道开放剂）10 mg/kg。在另一组中，大鼠在接受高剂量法舒地尔之前接受 5-羟基癸酸 (5HD)（一种 m-KATP 通道阻滞剂），剂量为 10 毫克/公斤。心肌梗塞面积以危险面积 (AAR) 的百分比表示。在正常血糖下，与对照组（42±7%）相比，低剂量和高剂量法舒地尔和二氮嗪可减少心肌梗塞面积（分别为 AAR 的 23±8%、21±9% 和 21±10%）。在高血糖下，低剂量法舒地尔（40±11%）和二氮嗪（44±14%）不能发挥这种有益作用，但高剂量法舒地尔以与正常血糖（21±13%）下相同的方式减少心肌梗塞面积。 5HD 阻止法舒地尔诱导的心肌梗塞面积减少 (42 ± 13%)。 Fasudil 通过激活大鼠体内的 m-KATP 通道诱导 PostC 对抗心肌梗塞。尽管高血糖会减弱 PostC，但大剂量法舒地尔可以恢复心脏保护作用。
The current study was carried out to determine whether fasudil hydrochloride (fasudil), a Rho-kinase inhibitor, has myocardial postconditioning (PostC) activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP) channels. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg) or high-dose (0.5 mg/kg) fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD), an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR). Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 ± 8%, 21 ± 9% and 21 ± 10% of AAR, respectively) compared with that in the control (42 ± 7%). Under hyperglycemia, low-dose fasudil (40 ± 11%) and diazoxide (44 ± 14%) could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 ± 13%). 5HD prevented fasudil-induced reduction of myocardial infarct size (42 ± 13%). Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.
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影响因子：
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通讯作者：
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