脳虚血時の脂質動態に及ぼすペントバルビタールの影響

EFFECTS OF PENTOBARBITAL ON BRAIN LIPID METABOLISM DURING GLOBAL ISCHEMIA

　抄録　ラットにペントバルビタールを60mg／kg前投与し，断頭法により全脳虚血を作製し，脳組織内脂質動態を経時的に観察することにより，その作用機序について検討を加えた。虚血により脳組織内には遊離脂肪酸が急激に増加蓄積するが，ペントバルビタール投与群では対照群と比べ，遊離脂肪酸の増加は有意に抑制され，特にステアリン酸とアラキドン酸の抑制が有意であった。また，ジグリセリドも虚血により脳内に増加するが，その脂肪酸組成は遊離してくる脂肪酸の組成に類似していた。さらに，この増加もペントバルビタール投与により，対照群に比し有意に抑制され，特にステアリン酸とアラキドン酸に富んだジグリセリドの増加抑制が顕著であった。これらの結果は，ペントバルビタールが，実験的脳虚血においてホスホリパーゼCの活性に影響を与え，脳内イノシトールリン脂質の分解に抑制的に作用している可能性が示唆され，この薬剤の生体膜安定化，脳保護の作用の一部を担っているものと推測された。

It is known that pentobarbital, which has been used for severe brain infarct or head injury as a brain protective drug, inhibits the increase of free fatty acids (FFAs) liberated from membrane phos-pholipids during ischemia. However, the mecha-nisms of FFA liberation from phospholipids and the mode of action of pentobarbital are still un-clear. Therefore we have investigated the effects of induction of global ischemia and pentobarbital pretreatment upon lipid metabolism in rat brain.

Brain ischemia was evoked by rat decapitation and pentobarbital (60mg/kg) was administered i.p. for 15 min prior to decapitation. Removed brains were incubated for 1, 5, 15 or 30min at 37℃ and then quickly frozen in liquid nitrogen. After ex-traction of lipids from the brains, neutral lipid and phospholipid compositions were analyzed by thin-layer and gas-liquid chromatography.

The results demonstrated that FFAs, either unsa-turated or saturated, were rapidly accumulated in the brain during early period of ischemia, but atte-nuated significantly by pentobarbital pretreatment. Pentobarbital attenuated the accumulations of ste-aric and arachidonic acids, with little effect on palmitic and oleic acids. Diacylglycerol (DG), which is considered to be as a plausible candidate for the source of FFA, was also produced in the ischemic brain, and its acyl chain composition was similar to that of liberated FFAs. Furthermore, the increase of DG was inhibited significantly by pen-tobarbital anesthesia. In particular, pentobarbital attenuated the accumulation of DG enriched in arachidonic and stearic acids. This fatty acyl com-position resembled the principal composition of phosphatidylinositol (PI) in rat brain. These obser-vations suggest that phospholipase C plays a cru-cial role in accumulation of FFAs and DG during ischemia, and pentobarbital may somehow alter phospholipase C activity and has some inhibitory effect on inositol phospholipid breakdown. Thus, it is considered that this inhibitory effect would exert a membrane stabilizing action and may in part explain the brain protective action of pentobarbital during ischemia.