一氧化氮在青霉素致痫中的作用及与NMDA和非NMDA受体的关系  

Role of nitric oxide in penicillin induced epileptic seizure and its relation with NMDA and non NMDA receptors on rat hippocampal slices

作　　者：陆巍[1] 陈刚[1] 程介士[1] 

机构地区：[1]上海医科大学神经生物学教研室医学神经生物学国家重点实验室

出　　处：《中国药理学通报》1998年第4期318-322,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金

摘　　要：目的阐明一氧化氮（ｎｉｔｒｉｏｘｉｄｅ，ＮＯ）在青霉素致痫中的作用及与ＮＭＤＡ及非ＮＭＤＡ受体的关系。方法用自制的一氧化氮敏感电极——Ｎａｆｉｏｎ－壳聚糖合镍修饰铂电极（Ｎａｆｉｏｎ－ＣＴＳ（Ｎｉ）－Ｐｔ）连续测定了青霉素致痫海马脑片ＣＡ１区锥体层神经元ＮＯ的释放，并同时观察了Ｎ－ｍｅｔｈｙｌ－Ｄ－ａｓｐａｒａｔｅ（ＮＭＤＡ）受体阻断剂ＤＬ－２－ａｍｉｎｏ－ｐｈｏｓｐｈｏ－ｎｏ－ｖａｌｅｒｉｃａｃｉｄ（ＡＰ５）及非ＮＭＤＡ／ＡＭＰＡ受体阻断剂６，７－ｄｉｎｉ－ｔｒｏｑｕｉｎｏｘａｌｉｎｅ－２，３（１ｈ，４ｈ）－ｄｉｏｎｅ（ＤＮＱＸ）对诱发痫波及ＮＯ含量的影响。结果①自制ＮＯ敏感电极检测ＮＯ浓度线性范围为４．５×１０－４～１．０×１０－８ｍｏｌ·Ｌ－１，检测下限为５．０×１０－８ｍｏｌ·Ｌ－１；②青霉素致痫时ＮＯ释放增加，与诱发脑片痫波有剂量反应关系；③ＮＭＤＡ受体阻断剂ＡＰ５（５０μｍｏｌ·Ｌ－１）明显抑制电刺激Ｓｃｈａｆｅｒ＇ｓ纤维引起的ＣＡ１区诱发痫波，表现为痫波数减少，同时伴有ＮＯ释放下降；④非ＮＭＤＡ受体阻断剂ＤＮＱＸ（３μｍｏｌ·Ｌ－１）对诱发痫波作用不明显，ＮＯ释放亦无显著变化；⑤ＡＰ５与一氧化?AIM To elucidate the potential role of excitatory amino acid receptor (NMDA, non NMDA) and nitric oxide (NO) in epileptogenesis; METHODS We observed the effect of N- methyl -D-asparate(NMDA) blocker DL 2 amino phospho novaleric acid(AP5) and 6,7 dinitroquinoxaline 2,3(1 h,4 h) dione(DNQX) on penicillin treated hippocampal slices by simultaneously recording evoked field potentials and nitric oxide release from CA1 pyramidal neurons, using self made NO sensitive microelectrode(SNM) microplatinum electrode modified with chitosan nickel(Ⅱ)complex and Nafion(Nafion CTS(Ni) Pt). RESULTS ① The linear relationship range and detection limit value of SNM were 4 5×10 -4 ～1 0×10 -8 mol·L -1 and 5 0×10 -8 mol·L -1 respectively; ② Penicillin (PEN) could elevate NO release, stimulus evoked field potential spikes(SEPS) in concentration dependent manner; ③ Both 7 NI and L NNA depressed NO release and partly reversed PENs epieptogenetic effect; ④APV, not DNQX, decreased NO release, partially antagonized PENs effect; but APV+7 NI+ L NNA did not display further inhibitory effect.CONCLUSION These findings suggest both anticonvulsant effect of NOS inhibitors and NMDA blockers, providing direct evidence for NO release in response to NMDA receptor activation. The anticonvulsant effect of NMDA blocker may conelate with its action on NO release.

关 键 词：青霉素 癫痫 NMDA受体 一氧化氮 致痫作用 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R978.11[医药卫生—临床医学]