虚血性脳障害に及ぼす麦角alkaloid誘導体Nicergolineの影響

Nicergoline, an Ergot Alkaloid, Improves Ischemic Brain Damage by Ameliorating the Decreased Cerebral Blood Flow and Metabolism in Spontaneously Hypertensive Rats

　麦角alkaloid誘導体nicergoline（NIC）の虚血性脳障害に及ぼす影響について，高血圧自然発症ラットの両側頸動脈結紮（BCAO）による虚血モデルを用い，生存率，脳水分含量，局所脳血流量（LCBF）およびブドウ糖代謝（LCGU）の面から検討した。永久BCAO後24時間における生存率は，NIC 8ないし16 mg／kg腹腔内投与により32％，38％（p＜0.05）と，非治療（saline群）の12％より高値となった。一方，BCAO3時間後において，NIC 100μg／kg／min静脈内持続投与は間脳・中脳領域の局所脳血流量（LCBF：¹⁴C—iodoantipyrine法）の低下を軽減し，また同領域の脳水分含量（乾燥重量法）の増加を軽減した。さらに，BCAO 3時間後再灌流2時間において，NIC投与はLCBFの低下および局所脳ブドウ糖代謝（¹⁴C−2—deoxyglucose法）の低下を軽減した。以上から，NICは脳虚血後の神経学的障害（生存率），および一過性脳虚血後の低灌流・低代謝を軽減する作用を有することが分かった。

Effects of ergot alkaloids, nicergoline (NIC), on survival rate, brain water content, local cerebral blood flow (LCBF : ¹⁴C-iodoantipyrine) and glu-cose utilization (LCGU : ¹⁴C-2-deoxyglucose) were examined after bilateral carotid artery occlusion (BCAO) in spontaneously hypertensive rats. Two series of study were performed ; the permanentBCAO and 3-hr-BCAO study. After permanent BCAO, the survival rate at 24 hrs of 32% (8mg/kg, i.p.) or 38% (16mg/kg) in NIC group was higher than that in non-treated group (12%). At the end of 3-hr-BCAO, the increase in water content (dry-wet) in di-mesencephalon was less in NIC (100μg/ kg/min, i.v.) group than that in non-treated group. The decrease in LCBF in caudate-putamen (CP) , parietal cortex (PC) , thalamus (TH) , hypotha-lamus (HT), and substantia nigra (SN) were less in NIC group than those in non-treated group. At the 2-hr-reperfusion after 3-hr-BCAO, the decrease inLCBF in TH and HT were less in NIC group than those in non-treated group. The LCGU in sensory motor cortex, CP, PC, HT, inferior colliculus and pons-reticular were higher in NIC group than those in non-treated group. From these results, it is con-cluded that nicergoline may have ameliorative effects on survival rate related to the prevention of decreased cerebral blood flow and metabolism fol-lowing brain ischemia.