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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 typevoltagegat edcalciumchannel,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 dini troquinoxaline 2 ,3 dione ,DNQX)对其变化的影响。结果如下 :( 1)缺血 15min导致蛋白酪氨酸磷酸化水平明显下降 ,再灌引起包括 180kD蛋白在内的多种蛋白酪氨酸磷酸化水平快速 (再灌 15min)而持续 (至少 48h)升高 ;( 2 )脑缺血 15min ,再灌 6h ,蛋白酪氨酸磷酸化达最高水平 ,180kD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 180kD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 ,180kD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
To investigate the effects of ischemia / reperfusion on the protein tyrosine phosphorylation of hippocampal synaptosomes and the noncompetitive antagonist of NMDA receptor (NR) in Mongolian gerbil with bilateral carotid artery ligation (BCAO) Ketamine (KT), L type voltage-gated calcium channel (L-type VGCC) antagonist nifedipine (ND) and non-NR antagonist 6, Effect of dini troquinoxaline 2, 3 dione (DNQX) on its changes. The results were as follows: (1) The level of protein tyrosine phosphorylation was significantly decreased after 15 min ischemia, and the protein tyrosine phosphorylation level including 180 kD protein was rapidly (reperfusion for 15 min) (2) The protein tyrosine phosphorylation reached the highest level at 15 min after ischemia, and 180 kD protein tyrosine phosphorylation level was 18 times higher than sham-operated control group. (3) Injection of KT or ND had antagonistic effect on the increase of protein tyrosine phosphorylation induced by ischemia / reperfusion, but no effect of DNQX; (4) Immunoprecipitation and immunoprinting proved that 180kD protein was NR2B, And its protein expression in cerebral ischemia / reperfusion did not change. The results suggest that (1) cerebral ischemia / reperfusion induces an increase in tyrosine phosphorylation of NR2B and other proteins, activating NR channels and aggravating neuronal damage; (2) NR channels can not only be regulated by tyrosine phosphorylation, but also NR channels And L-type VGCC are involved in the regulation of protein tyrosine phosphorylation of NR2B after cerebral ischemia / reperfusion. The two channel antagonists may be useful in the prevention and treatment of ischemic brain injury