Bakalova Rumiana, Matsuura Tetsuia, Kanno Iwao
Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels, Akita 010-0874, Japan.
Exp Biol Med (Maywood). 2002 Jul;227(7):465-73. doi: 10.1177/153537020222700710.
The present study was designed to investigate whether administration of indomethacin (IMC), a non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, and Rofecoxib, a highly selective COX-2 inhibitor, affect the regulation of regional cerebral blood flow response evoked by somatosensory activation (evoked rCBF). IMC and Rofecoxib were applied intravenously (6.25 and 3 mg/kg/hr, respectively). Somatosensory activation was induced by electrical hind paw stimuli of 0.2, 1, and 5 Hz (5-sec duration, 1.5 mA). The evoked rCBF was measured in alpha-chloralose anesthetized rats using laser-Doppler flowmetry. Before and after drug application, the evoked rCBF showed a frequency-dependent increase in the range of 0.2-5 Hz stimulation. IMC reduced significantly (about 50%-60%) evoked rCBF in response to all frequencies of hind paw stimulation (P< 0.05). Rofecoxib reduced significantly (about 50%) evoked rCBF in response to 1 and 5 Hz stimulation (P< 0.05), but did not affect evoked rCBF at 0.2 Hz. After IMC or Rofecoxib application, the normalized evoked rCBF curves peaked earlier as compared with that before their application (P< 0.05), although the rise time of 0.5 sec was nearly constant regardless of the stimulus frequency. The termination time of evoked rCBF curves was changed significantly after IMC application at 0.2 Hz stimulation (P< 0.05), but was not affected after Rofecoxib application. Neither COX inhibitor significantly affected the baseline level of CBF. The results suggest a participation of COX products in the regulation of evoked rCBF in response to somatosensory stimulation in the brain.
本研究旨在调查非选择性环氧化酶（COX-1和COX-2）抑制剂吲哚美辛（IMC）及高选择性COX-2抑制剂罗非昔布是否会影响体感激活诱发的局部脑血流反应（诱发rCBF）的调节。IMC和罗非昔布通过静脉给药（分别为6.25和3 mg/kg/小时）。通过对后爪施加0.2、1和5 Hz的电刺激（持续5秒，1.5 mA）来诱发体感激活。使用激光多普勒血流仪在α-氯醛糖麻醉的大鼠中测量诱发rCBF。在给药前后，诱发rCBF在0.2 - 5 Hz刺激范围内呈现频率依赖性增加。IMC使后爪所有刺激频率下的诱发rCBF显著降低（约50% - 60%）（P < 0.05）。罗非昔布使1和5 Hz刺激下的诱发rCBF显著降低（约50%）（P < 0.05），但对0.2 Hz的诱发rCBF无影响。应用IMC或罗非昔布后，与用药前相比，归一化的诱发rCBF曲线峰值出现得更早（P < 0.05），尽管无论刺激频率如何，0.5秒的上升时间几乎恒定。在0.2 Hz刺激下应用IMC后，诱发rCBF曲线的终止时间发生显著变化（P < 0.05），但应用罗非昔布后未受影响。两种COX抑制剂均未显著影响CBF的基线水平。结果表明COX产物参与了大脑中体感刺激诱发的rCBF调节。
