Wakahara Nobuyuki, Katoh Hideki, Yaguchi Yasuhiro, Uehara Akihiko, Satoh Hiroshi, Terada Hajime, Fujise Yutaka, Hayashi Hideharu
Division of Cardiology, Department of Internal Medicine III, Hamamatsu University School of Medicine, Japan.
Circ J. 2004 Feb;68(2):156-62. doi: 10.1253/circj.68.156.
Recent studies have implicated the opening of mitochondrial K(ATP) (mitoK(ATP)) channels and the production of reactive oxygen species (ROS) in the cardioprotective mechanism of ischemic preconditioning (IPC).
The involvement of mitoK(ATP) channels and ROS in the cardioprotective effects of both IPC and the mitoK(ATP) channel opener diazoxide (DZ) was investigated in ischemic/reperfused rat hearts. The effects of IPC and DZ on myocardial high-energy phosphate concentrations and intracellular pH (pH(i)) were also examined using (31)P nuclear magnetic resonance spectroscopy. Although both the mitoK(ATP) channel inhibitor 5-hydroxydecanoate and the antioxidant N-acetylcysteine abolished the postischemic recovery of contractile function by DZ, neither of them inhibited that by IPC. IPC attenuated the decline in pHi during ischemia, but DZ did not (6.28+/-0.04 in IPC, p<0.05, and 6.02+/-0.05 in DZ vs 6.02 +/-0.06 in control hearts). DZ, but not IPC, reduced the decrease in ATP levels during ischemia (ATP levels at 20-min ischemia: 26.3+/-3.4% of initial value in DZ, p<0.05, and 8.1+/-3.0% in IPC vs 15.1+/-1.3% in control hearts).
These results suggest that DZ-induced cardioprotection is related to ROS production and reduced ATP degradation during ischemia, whereas attenuated acidification during ischemia is involved in IPC-induced cardioprotection, which is not mediated through mitoK(ATP) channel opening or ROS production.
最近的研究表明线粒体ATP敏感性钾通道（mitoK(ATP)）的开放及活性氧（ROS）的产生参与了缺血预处理（IPC）的心脏保护机制。
在缺血/再灌注大鼠心脏中研究了mitoK(ATP)通道和ROS在IPC及mitoK(ATP)通道开放剂二氮嗪（DZ）心脏保护作用中的参与情况。还使用磷-31核磁共振波谱法检测了IPC和DZ对心肌高能磷酸盐浓度及细胞内pH（pH(i)）的影响。虽然mitoK(ATP)通道抑制剂5-羟基癸酸和抗氧化剂N-乙酰半胱氨酸均可消除DZ所致的缺血后收缩功能恢复，但二者均不能抑制IPC所致的收缩功能恢复。IPC减轻了缺血期间pHi的下降，但DZ没有（IPC组为6.28±0.04，P<0.05；DZ组为6.02±0.05，而对照组心脏为6.02±0.06）。DZ而非IPC降低了缺血期间ATP水平的下降（缺血20分钟时的ATP水平：DZ组为初始值的26.3±3.4%，P<0.05；IPC组为8.1±3.0%，而对照组心脏为15.1±1.3%）。
这些结果提示，DZ诱导的心脏保护与缺血期间ROS的产生及ATP降解减少有关，而缺血期间酸化减轻参与了IPC诱导的心脏保护，这并非通过mitoK(ATP)通道开放或ROS产生介导。
