新型长春花生物碱衍生物长春西汀对大脑中动脉闭塞新大鼠模型葡萄糖利用及脑水肿的保护作用

Protective effect of vinconate, a novel vinca alkaloid derivative, on glucose utilization and brain edema in a new rat model of middle cerebral artery occlusion.

Araki T, Kato H, Kogure K

Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.

Gen Pharmacol. 1992 Jan;23(1):141-6. doi: 10.1016/0306-3623(92)90061-n.

Abstract

We investigated the effect of a novel vinca alkaloid derivative, vinconate, against brain damage after focal ischemia induced by a middle cerebral artery (MCA) occlusion in rats. 2. Persistent focal ischemia was induced by 6 hr, and vinconate (50 and 100 mg/kg) was given intraperitoneally twice 10 min and 3 hr after MCA occlusion. 3. Focal ischemia produced the disturbance of glucose metabolism, the increase of water content and the impairment of protein synthesis in the surrounding occluded MCA territory. 4. Vinconate was effective in preventing marked reduction of cerebral glucose utilization in the areas surrounding the occluded MCA territory. 5. Vinconate significantly reduced an increase of water content in the surrounding the occluded MCA territory. 6. Preliminary L-[methyl-14C]methionine autoradiographic study also indicated that vinconate can partly prevent a severe impairment of protein synthesis after focal ischemia. 7. The results indicate that vinconate may ameliorate the disturbance of glucose metabolism, brain edema and the impairment of protein synthesis after persistent focal ischemia, and they also suggest that vinconate has a beneficial effect against brain damage.

摘要

我们研究了一种新型长春花生物碱衍生物长春酸盐对大鼠大脑中动脉（MCA）闭塞所致局灶性缺血后脑损伤的影响。2. 通过6小时诱导持续性局灶性缺血，并在MCA闭塞后10分钟和3小时腹腔注射长春酸盐（50和100毫克/千克）两次。3. 局灶性缺血导致闭塞的MCA区域周围葡萄糖代谢紊乱、含水量增加和蛋白质合成受损。4. 长春酸盐可有效防止闭塞的MCA区域周围脑葡萄糖利用显著降低。5. 长春酸盐显著降低了闭塞的MCA区域周围含水量的增加。6. 初步的L-[甲基-14C]蛋氨酸放射自显影研究还表明，长春酸盐可部分预防局灶性缺血后蛋白质合成的严重受损。7. 结果表明，长春酸盐可能改善持续性局灶性缺血后的葡萄糖代谢紊乱、脑水肿和蛋白质合成受损，并且还提示长春酸盐对脑损伤具有有益作用。