Katayama Y, Fukuchi T, McKee A, Terashi A
Second Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113, Japan.
Brain Res. 1998 Jan 19;781(1-2):212-7. doi: 10.1016/s0006-8993(97)01246-8.
The purpose of this study was to determine if nicardipine, a calcium ion channel blocker, affects pyruvate dehydrogenase (PDH) activity and improves energy metabolism during cerebral ischemia and reperfusion. Cerebral ischemia was induced, using the bilateral carotid artery occlusion method, for 60 min followed by reperfusion up to 120 min in gerbils. Nicardipine (1 mg/kg) or saline (vehicle-treated) was given to gerbils 30 min prior to the occlusion of the common carotid arteries. PDH activity and metabolites (ATP, PCr, and lactate) were measured in cortex prior to ischemia, immediately following ischemia, and after each reperfusion period. After 60 min ischemia, PDH activity increased in both groups, and was significantly higher in the nicardipine-treated group. After 20 min reperfusion, PDH activity in the nicardipine-treated group recovered to control levels, whereas, the PDH activity in the vehicle-treated group remained elevated, and was higher than the nicardipine-treated animals. At 60 and 120 min reperfusion, the activities in the vehicle-treated group were significantly below control levels, there were no differences, however, between the two groups. ATP and PCr concentrations were markedly depleted immediately after ischemia in both groups. ATP levels at 20 min reperfusion and PCr levels at 60 min reperfusion were significantly higher in the nicardipine-treated group. Lactate concentrations in both groups increased 7-8 fold, similarly, immediately after ischemia. During reperfusion, the lactate remained elevated in both groups, though the levels in the nicardipine-treated group were lower than those in the vehicle-treated group, but not significantly. Nicardipine treatment normalized PDH activity quickly and improved energy metabolism after reperfusion.
本研究的目的是确定钙离子通道阻滞剂尼卡地平是否会影响丙酮酸脱氢酶（PDH）活性，并改善脑缺血及再灌注期间的能量代谢。采用双侧颈动脉闭塞法诱导沙土鼠脑缺血60分钟，随后再灌注120分钟。在双侧颈总动脉闭塞前30分钟，给沙土鼠注射尼卡地平（1毫克/千克）或生理盐水（溶剂处理）。在缺血前、缺血后即刻以及每个再灌注期后，测量皮质中的PDH活性和代谢产物（三磷酸腺苷、磷酸肌酸和乳酸）。缺血60分钟后，两组的PDH活性均升高，且尼卡地平治疗组显著更高。再灌注20分钟后，尼卡地平治疗组的PDH活性恢复至对照水平，而溶剂处理组的PDH活性仍升高，且高于尼卡地平治疗的动物。在再灌注60分钟和120分钟时，溶剂处理组的活性显著低于对照水平，但两组之间无差异。两组在缺血后即刻三磷酸腺苷和磷酸肌酸浓度均显著降低。尼卡地平治疗组在再灌注20分钟时的三磷酸腺苷水平和再灌注60分钟时的磷酸肌酸水平显著更高。两组的乳酸浓度在缺血后即刻均增加了7 - 8倍。在再灌注期间，两组的乳酸水平均保持升高，尽管尼卡地平治疗组的水平低于溶剂处理组，但差异不显著。尼卡地平治疗可使PDH活性迅速恢复正常，并改善再灌注后的能量代谢。
