Niwa M, Hara A, Iwai T, Sassa T, Mori H, Uematsu T
Department of Pharmacology, Gifu University School of Medicine, Japan.
Neurol Res. 1997 Dec;19(6):629-33. doi: 10.1080/01616412.1997.11740872.
To determine the effect of phencyclidine (a noncompetitive NMDA receptor antagonist) on expression of Bax and Bcl-2 (apoptosis-regulating proteins) in gerbil hippocampus after transient forebrain ischemia, brain sections were immunohistochemically evaluated 48, 72, 96 h and 7 days following ischemia. In ischemic control animals, the expression of Bax in CA1 neurons was increased with time and peaked at 72 h, then disappeared at 96 h. In the phencyclidine (5 mg kg-1, intraperitoneally)-treated animals, the intensity of Bax expression at 72 h was weaker than that of ischemic control animals. Furthermore, at 96 h, Bax expression was still observed in CA1 neurons. No expression of Bcl-2 in the CA1 neurons was detected in either control or phencyclidine-treated animals. From these results, it is possible that NMDA receptor antagonists exert their preventive effect against delayed neuronal death through inhibition of Bax protein expression, although the precise relationship between the function of Bax protein and delayed neuronal death is still unclear.
为了确定苯环利定（一种非竞争性N-甲基-D-天冬氨酸受体拮抗剂）对沙土鼠短暂性前脑缺血后海马中Bax和Bcl-2（凋亡调节蛋白）表达的影响，在缺血后48、72、96小时和7天对脑切片进行免疫组织化学评估。在缺血对照动物中，CA1神经元中Bax的表达随时间增加，并在72小时达到峰值，然后在96小时消失。在苯环利定（5mg/kg，腹腔注射）处理的动物中，72小时时Bax表达的强度低于缺血对照动物。此外，在96小时时，CA1神经元中仍观察到Bax表达。在对照动物或苯环利定处理的动物中，均未在CA1神经元中检测到Bcl-2的表达。从这些结果来看，尽管Bax蛋白功能与迟发性神经元死亡之间的确切关系仍不清楚，但N-甲基-D-天冬氨酸受体拮抗剂可能通过抑制Bax蛋白表达对迟发性神经元死亡发挥预防作用。
