実験的脳虚血に及ぼすbifemelaneの効果—遊離脂肪酸の蓄積に対する抑制

EFFECTS OF BIFEMELANE ON THE FREE FATTY ACID LEVELS DURING ISCHEMIA

　抄録　ラット脳虚血モデルを用い，bifemelaneの遊離脂肪酸に及ぼす効果について検討した。全身状態には有意の変化を認めなかった。遊離脂肪酸は虚血によって約2.7倍に増加した（p＜0.05）。Bifemelaneを虚血30分前に投与した群では15mg／kgでは対照群と有意差がなく，30mg／kgの用量では有意に蓄積が抑制された。個々の脂肪酸の中で16：0,18：0,18：1に対しての抑制効果が有意であったが，20：14，22：6に対しては効果を認めなかった。以上の成績から本剤の虚血前投与は脳エネルギー代謝の改善によって脂肪酸の再アシル化に寄与するものと推測された。

Using the four-vessel extracranial one staged occlusion model of adult Wistar rats, we analyzed quantitatively released free fatty acids during ischemia. Also have we analyzed the effect of bifemelane to reduce free fatty acid accumulation after the onset of ischemia. Bifemelane (15 mg/kg, 30 mg/kg) and saline as control were intraperi-toneally administred to adult Wistar rat prior to 30 minutes of experimentally induced ischemia.

The results obtained were analyzed by one or two way analysis of variance (ANOVA). Physio-logical variables (systemic arterial pressure, PaO₂, PaCO₂, pH) did not change significantly in all four experimental groups. Total free fatty acid levels (sum of 5 fatty acid) increased significantly after ischemia (30 minutes). Higher dose (30 mg/kg) of bifemelane administration significantly reduced total free fatty acid accumulation, though lower dose (15 mg/kg) did have no effect. Bifemelane (30 mg/kg) reduced significant accumulation in the amount of saturated and monounsaturated fatty acid (palmitic acid [16 : 0], stearic acid [18: 0] and oleic acid [18: 1]). Arachidonic (20: 4) and docosahexaenoic (22 : 6) acid failed to show any effective reduction by bifemelane pre-treatment of lower nor higher dose.

Bifemelane is supposed to have many pharmaco-logical effects such as increase in cerebral blood flow, augmentation of glucose uptake, monoamine metabolism, cerebral vasodilatation and platelet antiaggregation. Free fatty acid accumulation is effectively suppressed by the higher dose of bife-melane administration. Althouth the exact mecha-nism are not clearly identified by the result ob-tained in this experiment, selective inhibition of accumulation in saturated and monounsaturated fatty acids by bifemelane pretreatment may be obtained by the improvement of energy metabo-lism, which may help to reacylation of fatty acid into phospholipid.