实验性癫癎时海马内兴奋性氨基酸受体对内阿片肽基因表达的影响

Influence of Hippocampal Excitatory Amino Acid Receptors on Biosynthesis of Endogenous Opioid Peptides During Penicillin Induced Seizure

目的阐明在癫发作与发展中起着重要作用的脑内兴奋性氨基酸类递质和内阿片肽之间的关系。方法应用原位杂交方法观察了青霉素致及海马内微量注射ＮＭＤＡ受体阻断剂ＭＫ－８０１（５－ｍｅｔｈｙ１－１０，１１－ｄｉｈｙｄｒｏ－５Ｈ－ｄｉｂｅｎｚｏ［ａ，ｄ］ｃｙｃｌｏｈｅｐｔａｎ－５，１０－ｉｍｉｎｅｍａｌｅａｔｅ）和非ＮＭＤＡ受体阻断剂ＤＮＱＸ（６，７－ｄｉｎｉｔｒｏｑｕｉｎｏｘａｌｉｎｅ－２，３－ｄｉｏｎｅ）后，大鼠海马内前脑啡肽原和前强啡肽原ｍＲＮＡ表达的变化。结果在青霉素致４ｈ后，海马ＣＡ１区、ＣＡ３区、齿状回前脑啡肽原ｍＲＮＡ和海马ＣＡ３区、齿状回前强啡肽原ｍＲＮＡ的表达明显增加。在青霉素致前分别在海马内微量注射ＭＫ８０１（６μｇ）和ＤＮＱＸ（４μｇ），则在减弱发作的同时，海马内前脑啡肽原ｍＲＮＡ的表达明显减少，而前强啡肽原ｍＲＮＡ的表达继续增加。

Purpose To clarify the relationship between the hippocampal excitatory amino acids and endogenous opioid peptides involved in the pathogenesis of epilepsy. Methods In situ hybridization techniques were used to evaluate the influence of NMDA receptor antagonist MK-801(5-methyl-10,11-dihydro-5H-dibenzocycloheptan-5,10-iminemaleate) and non-NMDA receptor antagonist DNQX(6,7-dinitroquinoxaline-2,3-dione)microinjected into the hippocampus on preproenkephalin(PPE)mRNA and preprodynorphin(PPD)mRNA expression during penicillin induced epilepsy. Results From 4h after injecting penicillin into the hippocampus,hippocampal PPE mRNA and PPD mRNA levels were significantly enhanced.When MK-801 and DNQX were injected respectively into the hippocampus at 20min before administration of penicillin, there were the derease of PPE mRNA and further increase of PPD mRNA in the hippocampus. Conclusions NMDA receptor and non-NMDA receptor may regulated the biosynthesis of PPD and PPE in the hippocampus during seizure by alterations in gene expression.