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蛋白激酶C抑制剂H7对苯妥英钠所致大鼠周围神经急性神经毒性作用的预防

Prevention of the acute neurotoxic effects of phenytoin on rat peripheral nerve by H7, an inhibitor of protein kinase C.

作者信息

Raya A, Gallego J, Hermenegildo C, Puertas F J, Romero F J, Felipo V, Miñana M D, Grisolía S, Romá J

机构信息

Departament de Fisiologia, Facultat de Medicina i Odontologia, Universitat de València, Spain.

出版信息

Toxicology. 1992 Nov 15;75(3):249-56. doi: 10.1016/0300-483x(92)90006-z.

DOI:10.1016/0300-483x(92)90006-z
PMID:1333652
Abstract

The neurotoxic effects of a single dose of phenytoin (150 mg/kg body weight) alone or 30 min after H7 (a protein kinase C inhibitor) injection (20 mg/kg body weight) were investigated in terms of peripheral neuromuscular function and Na+,K(+)-ATPase activity of the sciatic nerve. This intraperitoneal injection of phenytoin induced complete blockade of muscle action potentials in the dorsal segmental muscles of the rat tail evoked by electric stimulation of the caudal nerve and a 40% decrease in the Na+,K(+)-ATPase activity of the rat sciatic nerve when compared with control values, measured as the difference between total and ouabain-insensitive ATPase activity. Prior administration of H7 resulted in the complete prevention of both effects. Implications of protein kinase C inhibition in phenytoin neurotoxicity are discussed.

摘要

研究了单剂量苯妥英(150毫克/千克体重)单独使用或在注射H7(一种蛋白激酶C抑制剂,20毫克/千克体重)30分钟后,对大鼠外周神经肌肉功能和坐骨神经钠钾ATP酶活性的神经毒性作用。腹腔注射苯妥英可导致电刺激尾神经时大鼠尾巴背节段肌肉动作电位完全阻断,与对照值相比,大鼠坐骨神经钠钾ATP酶活性降低40%,对照值通过总ATP酶活性与哇巴因不敏感ATP酶活性之差来测量。预先给予H7可完全预防这两种作用。文中讨论了蛋白激酶C抑制在苯妥英神经毒性中的意义。

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