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Effect of ischemia/reperfusion on the phosphorylation of synaptosomal tyrosine of hippocampus of Mongolian gerbils
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- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 2
- DOI:
- 10.3321/j.issn:0371-0874.2000.02.010
- Key Word:
- 脑缺血;氯胺酮;硝苯吡啶;6,7-二硝基喹恶啉上卫四;N-甲基-D-天冬氨酸受体;L-型电压门控钙通道;酪氨酸磷酸化;N-甲基-D-天冬氨酸受体2B亚基
Abstract： 用蒙古沙土鼠双侧颈总动脉结扎(BCAO)前脑缺血模型, 研究缺血/再灌对海马突触体蛋白酪氨酸磷酸化的影响及NMDA受体(NR)非竞争性拮抗剂氯胺酮(ketamine, KT)、 L-型电压门控钙离子通道(L-type voltage gated calcium channel, L-型VGCC)拮抗剂硝苯吡啶(nifedipine, ND)及非NR拮抗剂6,7-二硝基喹恶啉上卫四(6,7-dinitroquinoxaline-2,3-dione, DNQX)对其变化的影响.结果如下: (1) 缺血15 min导致蛋白酪氨酸磷酸化水平明显下降, 再灌引起包括180 kD蛋白在内的多种蛋白酪氨酸磷酸化水平快速(再灌15 min)而持续(至少48 h)升高;(2) 脑缺血15 min, 再灌6 h, 蛋白酪氨酸磷酸化达最高水平, 180 kD蛋白酪氨酸磷酸化水平为假手术对照组的1.8倍;(3) 缺血前腹腔注射KT或ND, 对缺血/再灌诱导180 kD等蛋白酪氨酸磷酸化水平升高均有拮抗作用, 但DNQX无此作用;(4) 免疫沉淀和免疫印渍证明, 180 kD 蛋白为NR2B, 且其蛋白表达在脑缺血/再灌时没有变化. 结果提示, (1) 脑缺血/再灌诱导NR2B等蛋白酪氨酸磷酸化增加, 激活NR通道, 加重神经元损伤;(2) NR通道不仅可被酪氨酸磷酸化调节, 而且NR通道和L-型VGCC都参与了脑缺血/再灌对NR2B等蛋白酪氨酸磷酸化水平的调节, 两种通道拮抗剂可能对防治缺血性脑损伤有一定作用.
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