低酸素脳における超微弱発光—第2報：mannitol,vitamin E,betamethasoneの脳保護作用

CHEMILUMINESCENCE ON HYPDXIC BRAIN:THE 2ND REPORT:CEREBRAL PROTECTIVE EFFECT OF MANNITOL, VITAMIN E AND BETAMETHASONE

　抄録　第1報にて，PaO₂　17〜22mmHg,5分間の低酸素を負荷したラット脳のchemiluminescence （CL）値が，負荷中から負荷解除後早期にかけて高値を示すことを報告した。今回は，vitamin E,glucocorticoid，mannitolおよびその併用が低酸素脳CL値にいかなる影響を及ぽすかを明らかにした。これらの薬剤を単独あるいは併用で前投与した場合のCL値は，無処置群に比べ有意な発光量の減少を示した。さらに各薬剤を添加した後のCL波長別強度の解析では，vitamin E,glucocorticoid添加によって全波長域におよぶスペクトル強度の減少が認められ，mannitol添加ではスペクトルに有意な変化がみられなかった。低酸素（PaO₂17〜22mmHg）負荷前に投与したvitamin E,glucocorticoid,mlannitolおよび三剤併用が，ラット脳のCL値を有意に減少せしめたことにより，三薬剤が生体内で発現する脂質過酸化に対して抑制的に作用することが示された。さらに，波長別の発光スペクトル分析の結果から，各薬剤が抑制する反応段階あるいは，捕捉するラジカルが異なることが示され，vitamin E,glucocorticoidは過酸化脂質崩壊過程を抑制し，mannitolは活性酸素を捕捉することが考えられる。

The effect of vitamin E, betamethasone and mannitol upon a series of pathological free radical reaction wihtin the hypoxic brain tissue was eva-luated by chemiluminescence method. The hypoxic brain was induced by arterial hypoxemia (PaO₂17-22mmHg) with normocapnia (PaCO₂ 28-38mm Hg) and normotension (MABP 100-140mmHg). 4% O₂-96% N2 mixed gas was used as the replace-ment for obtaining lowered PaO₂.

In the control group high valued chemilumines-cence was measured in the hypoxic state and in the early stage of the initial post-hypoxic state. In the groups administered vitamin E, betame-thasone, mannitol and combination of them, how-ever, just extra low valued chemiluminescence was detected.

Besides to explore the stage on which the drugs act in lipid peroxidation, chemiluminescence spec-tra was analyzed using the homogenate added the each drug. Intensity peaks of the spectra were around at 480, 520-530, 570, 620-640, 680-700 nmbefore addition of the drugs.

All the intensity peaks diminished after addition of vitamin E and betamethasone, while in case of mannitol, very little decrease of the intensity peaks was revealed.

These experimental results indicate as follows. The lowered chemiluminescence value may prove the possibility of vitamin E, betamethasone and mannitol as free radical scavengers or inhibitor of lipid peroxidation. Chemiluminescence spectro-analysis shows that vitamin E and betamethasone act on the break down of lipid hydroperoxide and mannitol act on hydroxy radical in lipid peroxida-tion.