Department of Pharmacology, Diabetes Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Pharmacol Res. 2010 Apr;61(4):342-8. doi: 10.1016/j.phrs.2009.11.009. Epub 2009 Dec 3.
Reactive oxygen species are important mediators that exert a toxic effect during ischemia-reperfusion (I/R) injury of various organs. Sulforaphane is known to be an indirect antioxidant that acts by inducing Nrf2-dependent phase 2 enzymes. In this study, we investigated whether sulforaphane protects heart against I/R injury. Sprague-Dawley rats received sulforaphane (500microg/kg/day) or vehicle intraperitoneally for 3 days and global ischemia was performed using isolated perfused Langendorff hearts. Hearts were perfused with Krebs-bicarbonate buffer for 20min pre-ischemic period followed by a 20min global ischemia and 50min reperfusion. Treatment with sulforaphane inhibited an increase in the post-ischemic left ventricular end-diastolic pressure (LVEDP) and improved the post-ischemic left ventricular developed pressure (LVDP), +/-dP/dt, and coronary flow as compared with the untreated control hearts. Pretreatment with 5-hydroxydecanoic acid (5-HD), a mitochondrial K(ATP) channel blocker, for 10min before ischemia attenuated the improvement of LVEDP, LVDP, +/-dP/dt, and coronary flow induced by sulforaphane. Sulforaphane markedly decreased the infarcted size and attenuated the increased lactate dehydrogenase level in effluent during reperfusion. Pretreatment with 5-HD also blocked these protective effects of sulforaphane. Post-ischemia increased the concentration of atrial natriuretic peptide in coronary effluent, which attenuated by sulforaphane treatment. Decreases on Mn-superoxide dismutase (SOD), catalase, and heme oxygenase-1 levels by I/R were increased by sulforaphane treatment and pretreatment of 5-HD blocked the sulforaphane effects. Increases in Bax and caspase-3 levels, and decrease in Bcl-2 level by I/R were attenuated by sulforaphane treatment. These results suggest that the protective effects of sulforaphane against I/R injury may be partly mediated through mitochondrial K(ATP) channels and antioxidant pathway.
活性氧是一种重要的介质，在各种器官的缺血再灌注（I/R）损伤中发挥毒性作用。已知萝卜硫素是一种间接抗氧化剂，通过诱导 Nrf2 依赖性相 2 酶发挥作用。在这项研究中，我们研究了萝卜硫素是否对心脏具有保护作用免受 I/R 损伤。Sprague-Dawley 大鼠每天腹膜内接受萝卜硫素（500μg/kg）或载体 3 天，并用分离的 Langendorff 心脏进行整体缺血。心脏在缺血前用 Krebs-碳酸氢盐缓冲液灌注 20min，随后进行 20min 整体缺血和 50min 再灌注。与未处理的对照心脏相比，萝卜硫素处理抑制了缺血后左心室舒张末期压（LVEDP）的升高，并改善了缺血后的左心室发展压（LVDP）、+/-dP/dt 和冠状血流。在缺血前 10min 用 5-羟基癸酸（5-HD）预处理，一种线粒体 K（ATP）通道阻滞剂，可减弱萝卜硫素引起的 LVEDP、LVDP、+/-dP/dt 和冠状血流的改善。萝卜硫素显着减少梗塞面积，并减轻再灌注期间流出液中乳酸脱氢酶水平的升高。5-HD 预处理也阻断了萝卜硫素的这些保护作用。缺血后，冠状流出液中心房利钠肽的浓度增加，萝卜硫素处理可减弱这种增加。萝卜硫素处理增加了 I/R 导致的 Mn-超氧化物歧化酶（SOD）、过氧化氢酶和血红素加氧酶-1 水平的降低，而 5-HD 预处理阻断了萝卜硫素的作用。I/R 引起的 Bax 和 caspase-3 水平的增加以及 Bcl-2 水平的降低被萝卜硫素处理所减弱。这些结果表明，萝卜硫素对 I/R 损伤的保护作用可能部分通过线粒体 K（ATP）通道和抗氧化途径介导。
