Brovincamine （BV 26-723）の急性期脳虚血に及ぼす効果：SHRSRの両側総頸動脈結紮モデルにおける検討

EFFECT OF BROVINCAMINE FUMARATE ON CEREBRAL ISCHEMIA ACUTELY INDUCED BY BLCL IN SHRSR

　抄録　Brovincamine （BV 26-723：BVと略す）の急性期脳虚血に及ぼす効果を検討した。対象は高血圧ラットであるSHRSR （16週齢，雄性）を用い，脳虚血の作成は両側総頸動脈結紮（BLCL）により行った。BV投与群は30mg／kgならびに60mg／kgの二つの群を作成し，対照群は生食投与とし，すべてBLCL前1時間およびBLCL直後に腹腔内へ投与した。BLCL前および3時間後まで水素クリアランス法により局所脳循環を経時的に測定した。BLCL 3時間後に脳代謝産物（ATP, lactate, pyruvate）および脳含水量を測定し，また，走査電顕を用いて脳血管を観察した。局所脳循環の検討においては，BV 30mg／kg投与群ではBLCL 2時間まで，60mg／kg投与群では3時間まで対照群に比べ有意に脳血流量の高値を示した。脳代謝の検討では，BV 30mg／kgおよび60mg／kgの両投与群とも対照群に比し，脳組織ATP値ならびにpyruvate値の有意な高値を示し，lactate値の有意な低値を示した。脳含水量では，BVの両投与群とも対照群に比べて有意な低下を認めた。脳血管の観察では，BV 30mg／kg投与群は対照群に比べ差異を認めなかったが，60mg／kg投与群では血管収縮およびmicrovilliの増生などの虚血性変化ならびに内皮細胞の傷害が抑制された。以上より，BVは急性期脳虚血においてその効果が期待できるものと考えられた。

The present study was designed to clarify the effect of brovincamine fumarate (BV 26-723 : BV) on the degree of cerebral ischemia acutely induced by bilateral common carotid artery ligation (BLCL) in stroke-resistant spontaneously hyper-tensive rats (SHRSR). BV was administered to SHRSR by intraperitoneal infusion (I. P.) of 30 mg/kg (BV 30 mg/kg group), 60 mg/kg (BV 60 mg/kg group) and 0.9% saline was similarly in-jected to SHRSR (control group) before and im-mediately after BLCL. Cerebral blood flow (rCBF) in the thalamus was measured by hydrogen clear-ance technique before and until 3 hr of BLCL periodically. The brain metabolites (ATP, lactate, pyruvate) were determined by the enzymatic me-thod and the brain water content was measured by freeze-dry method 3 hr after BLCL. The histo-pathological changes in brain vessels were ob-served by scanning electron microscopy (SEM) 3 hr after BLCL.

The rCBF of three groups were identical before BLCL. However, the rCBF of BV 30 mg/kg group was statistically higher than in control group until 2 hr after BLCL, and that of BV 60 mg/kg group was significantly higher even 3 hr after BLCL. In measurements of the brain metabolites after BLCL, ATP and pyruvate levels in both the BV 30 mg/kg and 60 mg/kg groups were statistically higher than the control group. And brain lactate concentrations in both the BV 30 mg/kg and 60 mg/kg groups were significantly lower than the control group. The brain water content of BV 30 mg/kg and 60 mg/kg groups were significantly lower then the control groupafter BLCL. From the observation of SEM in the brain vessels after BLCL, BV 60 mg/kg group showed a less propagation of microvilli on the endothelial surface than in control group. And the vasoconstriction was not observed in BV 60 mg/kg group, though there were no significant difference between BV 30 mg/kg group and con-trol group. Furthermore, in BV 60 mg/kg group the endothelial damage were remarkably less than in the other two groups.

These results indicated efficacy of administrating BV for the treatment of acute cerebral ischemia.