実験的脳虚血における脳内serotonin代謝とcoenzyme Q投与の効果について

BRAIN SEROTONIN METABOLISM IN EXPERIMENTAL CEREBRAL ISCHEMIA AND THE EFFECT OF COENZYME Q ADMINISTRATION

　抄録　われわれはラットの両側総頸動脈結紮による虚血脳モデルを用いて，虚血部の前脳，および椎骨脳底動脈により血流の保持された脳幹と小脳について経時的にserotonin濃度とその最終代謝産物である5—HIAA濃度を螢光定量法により測定した。次に，血液脳関門を通過し虚血下で電子伝達系を賦活するCo—enzyme Q （CoQ）に注目し，60分間の虚血脳に対するCoQ　前投与の効果を検討した。結果：①CoQ非投与群における60分間虚血後のserotonin濃度は前脳では有意（p＜0.001）に低下し，脳幹と小脳では滅少傾向を示した。5—HIAA濃度は前脳と小脳では有意な変化を示さず，脳幹でも軽度の減少傾向を示すにとどまつた。②sham operation群にCoQ前投与すると，脳内serotonin,5—HIAA濃度は脳幹においてのみ増加傾向を示した。③CoQ前投与群に60分間脳虚血を施行すると，serotonin濃度はCoQ非投与群に比較し，脳幹（P＜0.01）と小脳（P＜0.05）において，また，5—HIAA濃度は脳幹（P＜0.05）において有意に上昇した。④以上より，CoQ前投与は脳内serotonin代謝動態を賦活するが，その効果は脳虚血下において，より明瞭に発揮されると思われた。

Bilateral ligation of common carotid arteries of male Wistar rats was produced during fasting for the periods of 15, 30 and 60 min. Thereafter the animals were killed by decapitation, and the brain was divided into the forebrain (ischemic portion), and the brain stem and the cerebellum (blood flow maintained portions by the vertebrobasilar ar-tery system). The above three portions were sub-jected to fluorophotometry of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) accord-ing to the method described by Curzon.

In the different series of the studies, rats pre-treated with coenzyme Q (CoQ) were exposed to bilateral ligation of common carotid arteries for 60 min, and the CoQ effect upon the serotonin metabolism was investigated.

The results obtained were as follows ;

1. The 5-HT levels in the forebrain progres-sively reduced starting at 15 min (p<0. 01), and reached to 80.2% of the control value at 60 min (p<0. 001), while those of the brain stem and the cerebellum showed no significant changes.

2. The time-course changes of 5-HIAA levels up to 60 min were not remarkable in the fore-brain and the cerebellum, while those of brain stem revealed a decreasing tendency.

3. CoQ pretreatment to sham-operated rats dis-closed a gross increasing trend of 5-HT and 5- HIAA concentrations in the brain stem.

4. CoQ preadministrated brains, of which bi-lateral common carotid arteries were ligated for 60 min, showed a statistically significant elevation of the 5-HT in the brain stem (p<0. 01) and in the cerebellum (p<0. 05), while the 5--HIAA level of CoQ preadministrated brains was higher only in the brain stem as compared to that of sham-operated rats (p<0. 05),

5. The above results would lead to the hypo-thesis that CoQ treatment could activate brain serotonin metabolism in case of cerebral infarct.