Sun D, Kintner D, Fitzpatrick J H, Emoto S E, Braquet P G, Bazan N G, Gilboe D D
Dept. of Neurological Surgery, University of Wisconsin, Madison 53706.
Neurochem Res. 1994 Apr;19(4):525-8. doi: 10.1007/BF00967333.
The effects of the platelet-activating factor antagonist BN 50739 and a free radical scavenger dimethyl sulfoxide on the accumulation of free fatty acids in post-ischemic canine brain are reported. Following 14 min of complete normothermic ischemia and 60 min of reperfusion, the total brain FFAs were approximately 150% higher than in the control group (p < 0.05). Perfusion with the platelet-activating factor antagonist BN50739 in its diluent dimethyl sulfoxide during 60 min of post-ischemic reoxygenation resulted in a 61.8% (p < 0.01) reduction in the total brain free fatty acid accumulation. Palmitic, stearic, oleic, linoleic, and arachidonic acids decreased by 53.8%, 63.5%, 69.0%, 47.4%, and 57.2%, respectively. Although dimethyl sulfoxide alone caused stearic and arachidonic acids to return to the normal concentration range, BN 50739 had a significant influence on recovery of palmitic, oleic, and linoleic acids and was previously shown to provide significant therapeutic protection against damage to brain mitochondria following an ischemic episode. Because free fatty acid accumulation is one of the early phenomena in cerebral ischemia, this study provides evidence to support the hypothesis that both platelet-activating factor and free radicals are involved in initiating cerebral ischemic injury.
报道了血小板活化因子拮抗剂BN 50739和自由基清除剂二甲基亚砜对缺血后犬脑游离脂肪酸蓄积的影响。在完全常温缺血14分钟和再灌注60分钟后，全脑游离脂肪酸总量比对照组高约150%（p<0.05）。在缺血后复氧60分钟期间，用其稀释剂二甲基亚砜灌注血小板活化因子拮抗剂BN50739，可使全脑游离脂肪酸蓄积减少61.8%（p<0.01）。棕榈酸、硬脂酸、油酸、亚油酸和花生四烯酸分别减少了53.8%、63.5%、69.0%、47.4%和57.2%。虽然单独使用二甲基亚砜可使硬脂酸和花生四烯酸恢复到正常浓度范围，但BN 50739对棕榈酸、油酸和亚油酸的恢复有显著影响，并且先前已证明其对缺血发作后脑线粒体损伤具有显著的治疗保护作用。由于游离脂肪酸蓄积是脑缺血的早期现象之一，本研究为支持血小板活化因子和自由基均参与引发脑缺血损伤这一假说提供了证据。
