脑缺血/再灌对蒙古沙土鼠海马突触体酪氨酸磷酸化的影响

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休的影响及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 ｇａｔｅｄｃａｌｃｉｕｍ ｃｈａｎｎｅｌ,Ｌ－型ＶＧＣＣ）拮抗剂硝苯吡啶（ｎｉｆｅｄｉｐｉｎｅ,ＮＤ）及非ＮＲ拮抗６,７－二硝基喹恶啉上卫四（６,７－ｄｉ－ｎｉｔｒｏｐｕ

Effect of ischemia/reperfusion on the phosphorylation of synaptosomal tyrosine of hippocampus of Mongolian gerbils

The effects of ischemia/reperfusion on the levels of protein tyrosine phosphorylation in the synaptosome of gerbil hippocampus and the effects of three drugs, ketamine (KT), a noncompetitive antagonist of NMDA receptor, nifedipine (ND), a voltage gated calcium channel (VGCC) antagonist and 6,7 di~ni~tro~qui~noxaline 2,3 dione (DNQX), a non NMDA receptor antagonist, on the phosphorylation were studied. The results showed that (1) 15 min of transient forebrain ischemia caused a marked decrease in the level of tyrosine phosphorylation of many protein bands, but, if followed by 15 min to 48 h of reperfusion, many protein bands including the 180 kD protein appeared to be increased; (2) the degree of tyrosine pho~sphory~lation of the protein bands was higher than that of the sham operated control, e g that of 180 kD protein was 1 8 fold of control; (3) administration of KT and ND before ischemia attenuated the increase of 180 kD protein tyrosine phosphorylation, while DNQX had no effect; and (4) immunoprecipitation and Western blot confirmed that the NR2B subunits of the NMDA receptors were among the phosphorylated 180 kD protein and ischemia /reperfusion did not affect the level of protein expression of NR2B. The above results suggest that the increase of tyrosine phosphorylation of NR2B induced by ischemia/reperfusion may further activate NR channels and aggravate neuronal injury, and that NR channels and other protein can be regulated by tyrosine phosphorylation not only through NR channels themselves but also via L type VGCCs. Consequently, antagonists of both NR channels and L type VGCCs may play a certain role in prevention and cure of ischemic brain injury.