Katayama Y, Kamiya T, Katsura K, Igarashi H, Fukuchi T
Second Department of Internal Medicine, Nippon Medical School.
Rinsho Shinkeigaku. 1999 Dec;39(12):1300-2.
Pyruvate dehydrogenase is one of the mitochondrial enzymes considered important in the regulation of oxidative metabolism. To further understand the relationship between its activity and ischemic brain damage we conducted three experiments. We studied the effects of (1) duration of cerebral ischemia, (2) the Ca2+ channel blocker, nicardipine, and (3) the immunosuppressant, FK506, on PDH activity and energy metabolites during ischemia and reperfusion. In the first study we also measured regional cerebral blood flow (rCBF). (1) Increasing the duration of the ischemic insult delayed the deactivation of PDH, slowed the resynthesis of high energy phosphates and the clearance of lactate, and impaired recovery of rCBF. Additionally, (2) nicardipine normalized PDH activities and improved the impaired metabolism after reperfusion, and (3) FK506 did not effect PDH activity, but significantly improved the impaired metabolism during the early phase of reperfusion. From these studies we conclude that PDH plays a role in the recovery of metabolism during reperfusion, and both nicardipine and FK506 improve metabolism during the early phase of reperfusion.
丙酮酸脱氢酶是线粒体酶之一，被认为在氧化代谢调节中很重要。为了进一步了解其活性与缺血性脑损伤之间的关系，我们进行了三项实验。我们研究了（1）脑缺血持续时间、（2）钙通道阻滞剂尼卡地平以及（3）免疫抑制剂FK506对缺血和再灌注期间丙酮酸脱氢酶活性及能量代谢产物的影响。在第一项研究中，我们还测量了局部脑血流量（rCBF）。（1）增加缺血损伤的持续时间会延迟丙酮酸脱氢酶的失活，减缓高能磷酸盐的重新合成和乳酸的清除，并损害rCBF的恢复。此外，（2）尼卡地平使丙酮酸脱氢酶活性恢复正常，并改善了再灌注后受损的代谢，并且（3）FK506对丙酮酸脱氢酶活性没有影响，但显著改善了再灌注早期受损的代谢。从这些研究中我们得出结论，丙酮酸脱氢酶在再灌注期间的代谢恢复中起作用，并且尼卡地平和FK506都能改善再灌注早期的代谢。
