苦参碱和槐定碱对神经可塑性的影响
|
摘要
苦豆子类生物碱是从药用植物苦豆子中提取分离纯化的一类生物碱,包括苦参碱、氧化苦参碱、槐定碱、槐果碱、槐胺碱、莱曼碱等共二十余种,他们均属于喹诺里西啶生物碱(Quinolizidine),化学结构相似。苦豆子类生物碱药理作用广泛,如解热、镇痛、抗炎、平喘、抗肿瘤以及抗心律失常等。在中枢作用方面,苦参碱和槐定碱分别是这类生物碱中具有抑制作用和兴奋作用的代表,有文献报道苦参碱具有镇静、镇痛以及降低体温等作用,而槐定碱则可兴奋中枢并诱发癫痫样反应。本实验以苦参碱和槐定碱为研究对象,采用神经电生理学方法观察了这两种药物对中枢神经突触可塑性的影响,并对槐定碱致癫痫样作用进行研究。
第一部分:苦参碱和槐定碱对神经可塑性的影响
目的:以苦参碱(matrine)和槐定碱(sophoridine)为研究对象,采用神经电生理学方法观察了这两种药物对中枢神经突触可塑性的影响。
方法:采用急性埋藏电极记录麻醉大鼠海马齿状回诱发电位的方法,以群峰电位峰值幅度(PS amplitude)和群体兴奋性突触后电位始段上升斜率(pEPSP slope)为观察指标,观察苦参碱和槐定碱对内侧穿行通路(MPP)-海马齿状回(DG)颗粒细胞这一神经通路联系上基础突触活动、LTP诱导以及双脉冲刺激反应的影响。苦参碱和槐定碱以腹腔注射(i.p.)形式给药,剂量分别为:苦参碱7.8、15.6、31.2mg/kg,槐定碱3、6、12mg/kg。引发LTP的条件刺激为60Hz、60个脉冲的高频刺激,双脉冲刺激实验按刺激间隔(IPIs)20～1000ms分别给出。
结果:(1)苦参碱能够显著抑制基础诱发电位中的PS幅度和pEPSP slope;能够显著抑制条件刺激(60 pulses at 60Hz)引发的LTP的PS幅度,但对pEPSP slope没有影响;纳洛酮能够翻转苦参碱在LTP诱导中的抑制作用;苦参碱对双脉冲刺激反应没有影响。(2)槐定碱能够明显增强基础诱发电位的PS幅度,但对pEPSP slope没有影响;能够促进条件刺激(60 pulses at 60Hz)引发的pEPSP slope LTP现象,但对PS幅度没有影响;槐定碱对双脉冲刺激反应有明显的抑制作用。
结论:(1)苦参碱对麻醉大鼠海马DG颗粒细胞的兴奋性和MPP-DG通路形成的突触联系过程均有抑制作用;对高频条件刺激诱发LTP后突触后颗粒细胞的兴奋性仍有抑制作用,但对条件刺激后突触的传递效能没有影响;纳洛酮能够翻转苦参碱在LTP诱导中对PS幅度LTP的抑制作用,提示苦参碱的抑制作用可能与激动中枢阿片受体有关;苦参碱对长时程突触可塑性的影响机制可能与短时程突触可塑性中的细胞和突触机制无关。(2)槐定碱对基础突触传递过程中海马DG颗粒细胞的兴奋性有促进作用,但对MPP-DG通路形成的突触联系过程没有影响;对高频刺激诱发LTP后突触后颗粒细胞的兴奋性没有影响,但对高频刺激诱发LTP后的突触传递过程有促进作用;槐定碱可能通过提高细胞外钙离子浓度和突触前递质释放几率而发挥其在双脉冲刺激反应中的抑制作用。
第二部分:槐定碱致癫痫样作用研究
目的:观察槐定碱(sophoridine)致痫大鼠清醒核团脑电(IEEG)变化特点;研究痫样特征分类,并利用工具药研究致痫作用机制。
方法:采用慢性埋藏电极记录清醒大鼠核团脑电(intracranial electroencephalography, IEEG)的方法,观察槐定碱对大鼠产生痫样放电的特点,并判断致痫原发部位;采用小鼠模型实施工具药拮抗实验,探讨槐定碱所致癫痫样发作的作用机制。
结果:海马齿状回(DG)内颗粒细胞对于槐定碱致痫作用最敏感,其次是内侧穿行通路(MPP)和颞叶皮层(TC)。阈下催眠剂量的地西泮、催眠剂量的巴比妥钠可以对抗槐定碱引起的痫样惊厥的发生;对抗最大电休克剂量的苯妥英钠不能对抗槐定碱引起的痫样惊厥的发生,但可以延缓惊厥的发生时间和小鼠的死亡时间。
结论:海马内部异常放电在槐定碱致痫作用中可能起到重要作用,海马部位可能是痫样发作的原发部位;槐定碱的致动物癫痫样发作属于临床小发作类型,地西泮是较理想的预防药物。
Sophora alopecuroides L. is a commonly used Chinese herbal drug. Matrine is one of the major active alkaloids isolated from the plant, and that including sophoridine, sophocarpine, oxymatrine, oxysophocarpine, sophoramine, etc., and lehmannine. It was previously reported that Sophora alopecuroides L. alkaloids have pharmacological effects, such as antipyretic, analgesic, antiasthma, anti-inflammatory, antivirus, and antitumor activity. However, the effect of this kind of alkaloids on neural synaptic plasticity has not been fully examined. Based on previous studies that they had inhibitory or excitatory effects on central nervous system, respectively, we choose the two of the alkaloids, matrine and sophoridine, to investigate their effects on the neural plasticity property in the MPP-DG circuit loop, and the epileptic seizure-like effect of sophoridine also been studied.
PART ONE
Object: To investigate the effects of matrine and sophoridine on neural plasticity in the PP-DG circuit loop, including the basal synaptic transmission, the induction of LTP, and the responses to the paired-pulse stimulation in anaesthetized rats.
Method: Perforant path evoked field potentials were recorded in the dentate gyrus by acutely implanted electrodes. Two parameters, the slope of population excitatory postsynaptic potential (pEPSP slope) and the amplitude of population spike (PS amplitude), were employed to evaluate the effects of drug. LTP was induced by high-frequency stimulation (60 pulses at 60 Hz) 30 min after intraperitoneal administration of matrine (7.8, 15.6, or 31.2mg/kg) or sophoridine (3, 6, or 12mg/kg). Pairs of stimulus pulses were delivered at interpulse intervals (IPIs) from 20 to 1000 ms.
Result: (1) Matrine can significantly inhibit the basal synaptic transmission both in population spike (PS) amplitude and the slope of population excitatory postsynaptic potential (pEPSP slope). Matrine can also inhibit the induction of LTP in PS amplitude, but had no significant effect on pEPSP slope. Matrine also had no significant effect on the responses to paired-pulse stimulation. The inhibitory effect of matrine on LTP induction was still observed when the rats were treated with atropine before hand. On the other hand, it was not observed after the rats were treated with naloxone previously. (2) Sophoridine can significantly increase the basal synaptic transmission in PS amplitude after intraperitoneal administration, but had no significant effect in pEPSP slope. Sophoridine can significantly increase pEPSP slope after LTP induction, but had no effect in PS amplitude. In addition, sophoridine had inhibitory effect on the response to paired-pulse stimulation.
Conclusion: The results suggest that matrine inhibits the basal synaptic transmission and long-term synaptic plasticity in PS amplitude, but not short-term synaptic plasticity in the dentate gyrus. Matrine exerts its inhibitory effect on LTP induction might be related to the activation of opioid receptors in DG. On the other hand, sophoridine can promote the basal synaptic transmission in PS amplitude and the induction of LTP in pEPSP slope. It is possible that increasing neurotransmitter release and elevating the efficacy of the synaptic process is partly responsible for the PPS inhibition induced by sophoridine.
PART TWO
Objective: To investigate the epileptic seizure-like effect of sophoridine on electro- encephalography (EEG) and its possible characteristic and the mechanism of the seizure-like effect.
Method: Chronic electron implantation was employed for IEEG recording in rat; and the traditional anti-seizure drugs were for the mechanism study in mice.
Result: Compared with the PP area and TC, the granule cell in DG is the most sensitive area in the kindling effect by s.c. sophoridine. Under- threshold hypnotic dosage of diazepam and the hypnotic dosage of pentobarbital sodium can block the sophoridine kinded seizure in mice, but the phenytoin sodium can not block the seizure, also the dosage in used can block MES seizure.
Conclusion: Sophoridine-induced synchronous oscillations in the hippocampus could elicit the generation and development of seizure. And the hippocampus might play the crucial role and be the original part of the seizure. Sophoridine kinded seizure might belong to clonic seizures, and diazepam is the ideal agent for the treatment.
第一部分:苦参碱和槐定碱对神经可塑性的影响
目的:以苦参碱(matrine)和槐定碱(sophoridine)为研究对象,采用神经电生理学方法观察了这两种药物对中枢神经突触可塑性的影响。
方法:采用急性埋藏电极记录麻醉大鼠海马齿状回诱发电位的方法,以群峰电位峰值幅度(PS amplitude)和群体兴奋性突触后电位始段上升斜率(pEPSP slope)为观察指标,观察苦参碱和槐定碱对内侧穿行通路(MPP)-海马齿状回(DG)颗粒细胞这一神经通路联系上基础突触活动、LTP诱导以及双脉冲刺激反应的影响。苦参碱和槐定碱以腹腔注射(i.p.)形式给药,剂量分别为:苦参碱7.8、15.6、31.2mg/kg,槐定碱3、6、12mg/kg。引发LTP的条件刺激为60Hz、60个脉冲的高频刺激,双脉冲刺激实验按刺激间隔(IPIs)20～1000ms分别给出。
结果:(1)苦参碱能够显著抑制基础诱发电位中的PS幅度和pEPSP slope;能够显著抑制条件刺激(60 pulses at 60Hz)引发的LTP的PS幅度,但对pEPSP slope没有影响;纳洛酮能够翻转苦参碱在LTP诱导中的抑制作用;苦参碱对双脉冲刺激反应没有影响。(2)槐定碱能够明显增强基础诱发电位的PS幅度,但对pEPSP slope没有影响;能够促进条件刺激(60 pulses at 60Hz)引发的pEPSP slope LTP现象,但对PS幅度没有影响;槐定碱对双脉冲刺激反应有明显的抑制作用。
结论:(1)苦参碱对麻醉大鼠海马DG颗粒细胞的兴奋性和MPP-DG通路形成的突触联系过程均有抑制作用;对高频条件刺激诱发LTP后突触后颗粒细胞的兴奋性仍有抑制作用,但对条件刺激后突触的传递效能没有影响;纳洛酮能够翻转苦参碱在LTP诱导中对PS幅度LTP的抑制作用,提示苦参碱的抑制作用可能与激动中枢阿片受体有关;苦参碱对长时程突触可塑性的影响机制可能与短时程突触可塑性中的细胞和突触机制无关。(2)槐定碱对基础突触传递过程中海马DG颗粒细胞的兴奋性有促进作用,但对MPP-DG通路形成的突触联系过程没有影响;对高频刺激诱发LTP后突触后颗粒细胞的兴奋性没有影响,但对高频刺激诱发LTP后的突触传递过程有促进作用;槐定碱可能通过提高细胞外钙离子浓度和突触前递质释放几率而发挥其在双脉冲刺激反应中的抑制作用。
第二部分:槐定碱致癫痫样作用研究
目的:观察槐定碱(sophoridine)致痫大鼠清醒核团脑电(IEEG)变化特点;研究痫样特征分类,并利用工具药研究致痫作用机制。
方法:采用慢性埋藏电极记录清醒大鼠核团脑电(intracranial electroencephalography, IEEG)的方法,观察槐定碱对大鼠产生痫样放电的特点,并判断致痫原发部位;采用小鼠模型实施工具药拮抗实验,探讨槐定碱所致癫痫样发作的作用机制。
结果:海马齿状回(DG)内颗粒细胞对于槐定碱致痫作用最敏感,其次是内侧穿行通路(MPP)和颞叶皮层(TC)。阈下催眠剂量的地西泮、催眠剂量的巴比妥钠可以对抗槐定碱引起的痫样惊厥的发生;对抗最大电休克剂量的苯妥英钠不能对抗槐定碱引起的痫样惊厥的发生,但可以延缓惊厥的发生时间和小鼠的死亡时间。
结论:海马内部异常放电在槐定碱致痫作用中可能起到重要作用,海马部位可能是痫样发作的原发部位;槐定碱的致动物癫痫样发作属于临床小发作类型,地西泮是较理想的预防药物。
Sophora alopecuroides L. is a commonly used Chinese herbal drug. Matrine is one of the major active alkaloids isolated from the plant, and that including sophoridine, sophocarpine, oxymatrine, oxysophocarpine, sophoramine, etc., and lehmannine. It was previously reported that Sophora alopecuroides L. alkaloids have pharmacological effects, such as antipyretic, analgesic, antiasthma, anti-inflammatory, antivirus, and antitumor activity. However, the effect of this kind of alkaloids on neural synaptic plasticity has not been fully examined. Based on previous studies that they had inhibitory or excitatory effects on central nervous system, respectively, we choose the two of the alkaloids, matrine and sophoridine, to investigate their effects on the neural plasticity property in the MPP-DG circuit loop, and the epileptic seizure-like effect of sophoridine also been studied.
PART ONE
Object: To investigate the effects of matrine and sophoridine on neural plasticity in the PP-DG circuit loop, including the basal synaptic transmission, the induction of LTP, and the responses to the paired-pulse stimulation in anaesthetized rats.
Method: Perforant path evoked field potentials were recorded in the dentate gyrus by acutely implanted electrodes. Two parameters, the slope of population excitatory postsynaptic potential (pEPSP slope) and the amplitude of population spike (PS amplitude), were employed to evaluate the effects of drug. LTP was induced by high-frequency stimulation (60 pulses at 60 Hz) 30 min after intraperitoneal administration of matrine (7.8, 15.6, or 31.2mg/kg) or sophoridine (3, 6, or 12mg/kg). Pairs of stimulus pulses were delivered at interpulse intervals (IPIs) from 20 to 1000 ms.
Result: (1) Matrine can significantly inhibit the basal synaptic transmission both in population spike (PS) amplitude and the slope of population excitatory postsynaptic potential (pEPSP slope). Matrine can also inhibit the induction of LTP in PS amplitude, but had no significant effect on pEPSP slope. Matrine also had no significant effect on the responses to paired-pulse stimulation. The inhibitory effect of matrine on LTP induction was still observed when the rats were treated with atropine before hand. On the other hand, it was not observed after the rats were treated with naloxone previously. (2) Sophoridine can significantly increase the basal synaptic transmission in PS amplitude after intraperitoneal administration, but had no significant effect in pEPSP slope. Sophoridine can significantly increase pEPSP slope after LTP induction, but had no effect in PS amplitude. In addition, sophoridine had inhibitory effect on the response to paired-pulse stimulation.
Conclusion: The results suggest that matrine inhibits the basal synaptic transmission and long-term synaptic plasticity in PS amplitude, but not short-term synaptic plasticity in the dentate gyrus. Matrine exerts its inhibitory effect on LTP induction might be related to the activation of opioid receptors in DG. On the other hand, sophoridine can promote the basal synaptic transmission in PS amplitude and the induction of LTP in pEPSP slope. It is possible that increasing neurotransmitter release and elevating the efficacy of the synaptic process is partly responsible for the PPS inhibition induced by sophoridine.
PART TWO
Objective: To investigate the epileptic seizure-like effect of sophoridine on electro- encephalography (EEG) and its possible characteristic and the mechanism of the seizure-like effect.
Method: Chronic electron implantation was employed for IEEG recording in rat; and the traditional anti-seizure drugs were for the mechanism study in mice.
Result: Compared with the PP area and TC, the granule cell in DG is the most sensitive area in the kindling effect by s.c. sophoridine. Under- threshold hypnotic dosage of diazepam and the hypnotic dosage of pentobarbital sodium can block the sophoridine kinded seizure in mice, but the phenytoin sodium can not block the seizure, also the dosage in used can block MES seizure.
Conclusion: Sophoridine-induced synchronous oscillations in the hippocampus could elicit the generation and development of seizure. And the hippocampus might play the crucial role and be the original part of the seizure. Sophoridine kinded seizure might belong to clonic seizures, and diazepam is the ideal agent for the treatment.
引文
1. Abe K, Nakata A, Mizutani A, Saito H. (1994) Facilitatory but nonessential role of the muscarinic cholinergic system in the generation of long-term potentiation of population spikes in the dentate gyrus in vivo. Neuropharmacology. 33(7):847-852.
2. Abe K, Yamaguchi S, Sugiura M, Saito H. (1999) The ethanol metabolite acetaldehyde inhibits the induction of long-term potentiation in the rat dentate gyrus in vivo. Br J Pharmacol. 127(8):1805-1810.
3. Abraham WC, Gustafsson B, Wigstr?m H. (1987) Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J Physiol. 394:367-380.
4. Albertson TE, Joy RM. (1987) Increased inhibition in dentate gyrus granule cells following exposure to GABA-uptake blockers. Brain Res. 435(1-2):283-292.
5. Andersen P, Bliss TV, Skrede KK. (1971) Unit analysis of hippocampal polulation spikes. Exp Brain Res. 13(2):208-221.
6. Bliss TVP, Collingridge GL. (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 361(6407): 31-39.
7. Bliss TV, Gardner-Medwin AR. (1973a) Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol. 232(2):357-374.
8. Bliss TV, Lomo T. (1973b) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 232(2):331-356.
9. Bramham CR, Milgram NW, Srebro B. (1991) Delta opioid receptor activation is required to induce LTP of synaptic transmission in the lateral perforant path in vivo. Brain Res. 567(1):42-50.
10. Bramham CR, Sarvey JM. (1996) Endogenous activation of mu and delta-1 opioid receptors is required for long-term potentiation induction in the lateral perforant path: dependence on GABAergic inhibition. J Neurosci. 16(24):8123-8131.
11. Burgard EC, Cote TE, Sarvey JM. (1993) Muscarinic depression of synaptic transmission and blockade of norepinephrine-induced long-lasting potentiation in the dentate gyrus. Neuroscience. 54(2):377-389.
12. Burwell RD, Witter MP, Amaral DG. (1995) Perirhinal and postrhinal cortices of the rat: a review of the neuroanatomical literature and comparison with findings from the monkey brain. Hippocampus. 5(5):390-408.
13. Charlton MP, Smith SJ, Zucker RS. (1982) Role of presynaptic calcium ions and channels in synaptic facilitation and depression at the squid giant synapse. J Physiol. 323:173-193.
14. Debanne D, Guérineau NC, G?hwiler BH, Thompson SM. (1996) Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release. J Physiol. 491 ( Pt 1):163-176.
15. Douglas RM, Goddard GV. (1975) Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus. Brain Res. 86(2):205-215.
16. Drake CT, Chavkin C, Milner TA. (2007) Opioid systems in the dentate gyrus. Prog Brain Res. 163:245-263.
17. Frotscher M, Léránth C. (1985) Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: a combined light and electron microscopic study. J Comp Neurol. 239(2):237-246.
18. Gaykema RP, Luiten PG, Nyakas C, Traber J. (1990) Cortical projection patterns of the medial septum-diagonal band complex. J Comp Neurol. 293(1):103-124.
19. Gilbert ME, Mack CM. (1999) Field potential recordings in dentate gyrus of anesthetized rats: stability of baseline. Hippocampus. 9(3):277-287.
20. Goodman LS et al. (1993) Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York, MacMillan, 213–214.
21. Halasy K, Somogyi P. (1993) Subdivisions in the multiple GABAergic innervation of granule cells in the dentate gyrus of the rat hippocampus. Eur J Neurosci. 5(5):411-429.
22. Hamid S, Dawe GS, Gray JA, Stephenson JD. (1997) Nicotine induces long-lasting potentiation in the dentate gyrus of nicotine-primed rats. Neurosci Res. 29(1):81-85.
23. Hessler NA, Shirke AM, Malinow R. (1993) The probability of transmitter release at a mammalian central synapse. Nature. 366(6455):569-572.
24. Higashiyama K, Takeuchi Y, Yamauchi T, Imai S, Kamei J, Yajima Y, et al. (2005) Implication of the descending dynorphinergic neuron projecting to the spinal cord in the (+)-matrine-and (+)-allomatrine-induced antinociceptive effects. Biol Pharm Bull. 28(5):845-848.
25. H?lscher C, Anwyl R, Rowan MJ. (1997) Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can Be depotentiated by stimulation on the negative phase in area CA1 in vivo. J Neurosci. 17(16):6470-6477.
26. H?lscher C. (1999) Synaptic plasticity and learning and memory: LTP and beyond. J Neurosci Res. 58(1):62-75.
27. Iga Y, Arisawa H, Ise M, Yasuda H, Takeshita Y. (1996) Modulation of rhythmical slow activity, long-term potentiation and memory by muscarinic receptor agonists. Eur J Pharmacol. 308(1):13-19.
28. Ikegaya Y, Saito H, Torii K, Nishiyama N. (1997) Activin selectively abolishes hippocampal long-term potentiation induced by weak tetanic stimulation in vivo. Jpn J Pharmacol. 75(1):87-89.
29. Joy RM, Albertson TE. (1993) NMDA receptors have a dominant role in population spike-paired pulse facilitation in the dentate gyrus of urethane-anesthetized rats. Brain Res. 604(1-2):273-282.
30. Kamei J, Xiao P, Ohsawa M, Kubo H, Higashiyama K, Takahashi H, Li J, Nagase H, Ohmiya S. (1997) Antinociceptive effects of (+)-matrine in mice. Eur J Pharmacol. 337(2-3):223-226.
31. Katz B, Miledi R. (1968) The role of calcium in neuromuscular facilitation. J Physiol. 195(2):481-492.
32. Korol DL, Gold PE. (2008) Epinephrine converts long-term potentiation from transient to durable form in awake rats. Hippocampus. 18(1):81-91.
33. Madison DV, Nicoll RA. (1988) Enkephalin hyperpolarizes interneurones in the rat hippocampus. J Physiol. 398:123-130.
34. McNaughton BL, Barnes CA. (1977) Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat. J Comp Neurol. 175(4):439-454.
35. Morris BJ, Johnston HM. (1995) A role for hippocampal opioids in long-term functional plasticity. Trends Neurosci. 18(8):350-355.
36. Moser EI. (1996) Altered inhibition of dentate granule cells during spatial learning in an exploration task. J Neurosci. 16(3):1247-1259.
37. Murthy VN, Sejnowski TJ, Stevens CF. (1997) Heterogeneous release properties of visualized individual hippocampal synapses. Neuron. 18(4):599-612.
38. Nadim F, Manor Y. (2000) The role of short-term synaptic dynamics in motor control. Curr Opin Neurobiol. 10(6):683-690.
39. Pang K, Williams MJ, Olton DS. (1993) Activation of the medial septal area attenuates LTP of the lateral perforant path and enhances heterosynaptic LTD of the medial perforant path in aged rats. Brain Res. 632(1-2):150-160.
40. Paxinos G and Watson C. The Rat Brain in Stereotaxic Coordinates. Academic press Australia (Second Edition 1986) and Academic press USA (Compact Third Edition 1997).
41. Racine RJ. (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 32(3):281-294.
42. Rose G, Diamond D, Lynch GS. (1983) Dentate granule cells in the rat hippocampal formation have the behavioral characteristics of theta neurons. Brain Res. 266(1):29-37.
43. Simmons ML, Terman GW, Drake CT, Chavkin C. (1994) Inhibition of glutamate release by presynaptic kappa 1-opioid receptors in the guinea pig dentate gyrus. J Neurophysiol. 72(4):1697-1705.
44. Squire LR, Stark CE, Clark RE. (2004) The medial temporal lobe. Annu Rev Neurosci. 27:279-306.
45. Straube T, Korz V, Balschun D, Frey JU. (2003) Requirement of beta-adrenergic receptor activation and protein synthesis for LTP-reinforcement by novelty in rat dentate gyrus. J Physiol. 552(Pt 3):953-60.
46. Taube JS, Schwartzkroin PA. (1988) Mechanisms of long-term potentiation: EPSP/spike dissociation, intradendritic recordings, and glutamate sensitivity. J Neurosci. 8(5):1632-1644.
47. Terman GW, Drake CT, Simmons ML, Milner TA, Chavkin C. (2000) Opioid modulation of recurrent excitation in the hippocampal dentate gyrus. J Neurosci. 20(12):4379-4388.
48. Terman GW, Wagner JJ, Chavkin C. (1994) Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus. J Neurosci. 14(8):4740-4747.
49. Thalmann RH, Ayala GF. (1982) A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus. Neurosci Lett. 29(3):243-248.
50. Tsodyks MV, Markram H. (1997) The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proc Natl Acad Sci U S A. 94(2):719-723.
51. Wagner JJ, Caudle RM, Chavkin C. (1992) Kappa-opioids decrease excitatory transmission in the dentate gyrus of the guinea pig hippocampus. J Neurosci. 12(1):132-141.
52. Wagner JJ, Terman GW, Chavkin C. (1993) Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus. Nature. 363(6428):451-454.
53. Williams S, Johnston D. (1988) Muscarinic depression of long-term potentiation in CA3 hippocampal neurons. Science. 242(4875):84-7.
54. Winson J, Dahl D. (1986) Long-term potentiation in dentate gyrus: induction by asynchronous volleys in separate afferents. Science. 234(4779):985-988.
55. Witter MP. (2007) The perforant path: projections from the entorhinal cortex to the dentate gyrus. Prog Brain Res. 163:43-61.
56. Yanagihashi R, Ishikawa T. (1992) Studies on long-term potentiation of the population spike component of hippocampal field potential by the tetanic stimulation of the perforant path rats: effects of a dopamine agonist, SKF-38393. Brain Res. 579(1):79-86.
57. Yin LL, Zhu XZ. (2005) The involvement of central cholinergic system in (+)-matrine-induced antinociception in mice. Pharmacol Biochem Behav. 80(3):419-425.
58. Zieglg?nsberger W, French ED, Siggins GR, Bloom FE. (1979) Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurons. Science. 205(4404):415-417.
59. Zucker RS. (1989) Short-term synaptic plasticity. Annu Rev Neurosci. 12:13-31.
60. Zucker RS. (1999) Calcium- and activity-dependent synaptic plasticity. Curr Opin Neurobiol. 9(3):305-313.
61.钟仁山,苦豆子的研究及其应用.第1版[M].银川:宁夏人民出版社, 1983:165
62.袁惠南,何汉增,尹玉琴等.苦参碱的中枢药理作用[J].浙江药学, 1986, 3(6):5-9
63.王绪平,陈庆梅,郑筱祥.苦参醇提取液镇静催眠作用的实验研究[J].中草药, 2004,35(5):551-553
64.王绪平,陈继平,章建民等.苦参碱对海马神经中枢抑制作用的研究[J].浙江中医杂志, 2007, 42(9):539-541
65.耿群美,李兰诚,贾晓英.苦参碱、氧化苦参碱对小鼠脑中递质γ-氨基丁酸和甘氨酸含量的影响[J].内蒙古医学院学报, 1992, 14(1):8-9
66.王秀坤,李家实.苦参碱等槐属六种生物碱对GABAA受体的作用[J].北京中医药大学学报, 2000, 23(supp):42-43
67.李玉香,白洁.槐定碱对大鼠皮层脑电的影响[J].中药药理与临床, 2007, 23(1):24-26.
68.胡淑婷,奥海航,陈晓霞等.槐定碱致痫大鼠模型的建立及血清TNF-α和IL-1β含量变化的研究[J].宁夏医学杂志, 2008, 30(12): 1065-1068
69.韩太真,突触可塑性与长时程增强现象的研究进展[J].西安交通大学学报(医学版), 2005, 26(4):305-308
70.贾凡,周逸峰.短时程突触可塑性的功能意义[J].生物化学与生物物理进展, 2000, 27(2): 174-177
71.许绍芬.神经生物学[M].上海:上海医科大学出版社, 1990: 262-268
72.梅镇彤.学习和记忆的神经生物学[M].上海:上海科技教育出版社, 1997:38-44
73.李雪梅,庄文华,姜鸷滋等.高剂量槐定碱对大鼠神经系统长期毒性的病理形态学观察[J].癌症, 2004, 23(11s): 1376-1378
74.陈晓霞,胡淑婷,杨雪琴等.槐定碱致痫大鼠海马Glu、GABA及血清中TNF、IL-2和IL-6含量变化的研究[J].宁夏医学院学报, 2007, 29(5): 944-945
75.彭晓东,许大庆,彭建中等.枸杞多糖对动物海马电活动的影响[J].宁夏医学院学报, 2002, 24(2): 79-81
76.肖培根.新编中药志(第一卷)[M].北京:化学工业出版社, 2002: 560
77.张晓丹,李显庆,邵碧霞,马灵芝.苦参碱的药代动力学及心血管作用研究进展[J].时针国医国药, 2006, 17(12): 2605-2606
78.王平全,陈曙霞,周贤飙,李丹,陆国红,陈美芳.苦参碱在大鼠体内的药物动力学[J].上海第二医科大学学报, 1996, 16(4): 250-252
79.庞志功,汪宝琪,王翔.口服苦参碱的药代动力学研究[J].西安医科大学学报, 1998, 19(2): 201
80.张守芳.中草药通讯[J]. 1977, 2: 39-41
81.黄圣凯,陈静芬,谢永新,袁惠南.槐定碱的气相色谱测定法及其在兔体内的药代动力学[J].药学学报, 1988, 23(8): 561-565
82.胡一中,黄圣凯.槐定碱的生理药动学模型[J].中国药理学与毒理学杂志, 1995, 9(2): 133-136
83.温玉麟.药物与化学物质毒性数据. [M].天津:天津科学技术出版社, 1989: 44
84.彭晓东,闫乾顺,闫琳等.鹅绒藤对小鼠抗惊厥作用的观察[J].第四军医大学学报, 2009, 30(4): 340-343
85.韩丹,张先荣,唐岳枫等.强直电刺激大鼠海马、中部颞叶新皮质诱发癫癇模型中电振荡与癫癇发生的关系研究[J].中国神经科学杂志, 2000, 16(2): 108-114
86.李雪梅,吴运光,潘达鑫等.新型抗肿瘤药槐定碱[J].中国新药杂志, 2006, 15(8): 654-657
87.余建强,蒋袁絮.槐定碱对大鼠中枢谷氨酸及氨基丁酸免疫阳性细胞的影响[J].中药药理与临床, 2006a, 22(2): 17-19
88.余建强,蒋袁絮.槐定碱对小鼠中枢神经系统的影响[J].中草药, 2006b, 37(11): 8861-8863
1.国家医药管理局中草药情报中心站编.植物药有效成分手册[M].北京,人民卫生出版社, 1985: 700.
2.刘梅,刘雪英,程建峰.苦参碱的药理研究[J].中国中药杂志, 2003, 28(9): 801-804.
3.钟仁山主编.苦豆子的研究及其应用[M].宁夏人民出版社, 1983出版.
4.袁惠南,何汉增,赵雅灵等.槐果碱对中枢神经系统的抑制作用[J].中药通报, 1987, 12(4): 45-47.
5.袁惠南,何汉增,尹玉琴等.苦参碱的中枢药理作用[J].浙江药学, 1986, 3(6): 5-9.
6.袁惠南,何汉增,赵雅灵等.槐胺碱对中枢神经系统的影响[J].西北药学杂志, 1986, 1(4): 12-14.
7.蒋袁絮,余建强,彭建中.氧化苦参碱对小鼠的中枢抑制作用[J].宁夏医学院学报, 2000, 22(3): 157-158.
8.余建强,蒋袁絮,彭建中.氧化槐定碱对小鼠中枢的抑制作用[J].华西药学杂志, 2001, 16(4): 277-278.
9.余建强,蒋袁絮,王丽韫.氧化槐定碱和氧化苦参碱对小鼠中枢的抑制作用[J].宁夏医学杂志, 2002, 24(1): 13-15.
10.耿群美,李兰诚,贾晓英.苦参碱、氧化苦参碱对小鼠脑中递质γ-氨基丁酸和甘氨酸含量的影响[J].内蒙古医学院学报, 1992, 14(1): 8-9.
11.王绪平,陈继平,章建民,陆建荣,洪学智.苦参碱注射液对小鼠脑海马氨基酸神经递质的作用研究[J].中成药, 2008, 30(8): 1218-1219.
12.王秀坤,李家实.苦参碱等槐属六种生物碱对GABAA受体的作用[J].北京中医药大学学报, 2000, 23(supp): 42-43.
13.王绪平,陈庆梅,郑筱祥.苦参醇提取液镇静催眠作用的实验研究[J].中草药, 2004, 35(5): 551-553.
14.陈庆梅,王绪平,张恒义,郑筱祥.群峰电位的定量分析及其在苦参碱研究中的应用[J].航天医学与医学工程, 2004, 17(4): 303-305.
15.王绪平,陈继平,章建民,陆建荣.苦参碱对海马神经中枢抑制作用的研究[J].浙江中医杂志, 2007, 42(9): 539-541.
16.罗学娅,张学梅,高卫,吴琴芳.苦参碱的镇痛作用部位及机制研究[J].中草药, 2001, 32(1): 41-43.
17.王百忍,赵经纬.一氧化氮与疼痛[J].神经解剖学杂志, 1995, 11(1): 69-74.
18.黄秀梅,李波.六种苦豆子生物碱对炎症介质白三烯的影响[J].中成药, 2003, 25(10): 8242-8261.
19. Kamei J, Xiao P, Ohsawa M, Kubo H, Higashiyama K, Takahashi H, et al. Antinociceptive effects of (+)-matrine in mice[J]. Eur J Pharmacol 1997; 337: 223-226.
20. Higashiyama K, Takeuchi Y, Yamauchi T, Imai S, Kamei J, Yajima Y, et al. Implication of the descending dynorphinergic neuron projecting to the spinal cord in the (+)-matrine-and (+)-allomatrine-induced antinociceptive effects[J]. Biol Pharm Bull 2005; 28(5): 845-848.
21. Lin-lin Yin, Xing-zu Zhu. The involvement of central cholinergic system in (+)-matrine-induced antinociception in mice[J]. Pharmacology, Biochemistry and Behavior 80 (2005): 419-425.
22.陈霞,刘芬,吕文伟等.氧化苦参碱的镇痛作用及其机制研究[J].中草药, 2006, 37(2): 255-257.
23.刘芬,刘洁,陈霞等.氧化苦参碱的镇痛作用及其机制[J].吉林大学学报(医学版), 2005, 31(6): 883-885.
24. Kobashi S, Kubo H, Yamauchi T, Higashiyama K. Antinociceptive effects of 1-acyl-4-dialkylaminopiperidine and 1-alkyl-4-dialkylaminopiperidine in mice: structure-activity relation study of matrine-type alkaloids[J]. Biol Pharm Bull 2002; 25(8): 1030-1034.
25.蔡本志,王玲,李春莉等.氧化苦参碱对大鼠海马神经元细胞钠通道的影响[J].哈尔滨医科大学学报, 2007, 41(2): 85-88.
26.张琳娜,白洁,刘红梅.氧化苦参碱对青霉素致痫大鼠的实验性研究[J].陕西中医, 2007, 28(6): 755-757.
27.胡淑婷,张志宁,陈晓霞,白洁.氧化苦参碱对青霉素致痫大鼠海马GABA、Glu及血清中细胞因子的影响[J].宁夏医学院学报, 2008, 30(6): 706-709.
28.白洁,张琳娜,胡淑婷,刘红梅.氧化苦参碱和槐定碱对青霉素致痫大鼠海马的影响[J].宁夏医学院学报, 2006, 28(6): 476-479.
29. Cho CH, Chuang CY, Chen CF. Study of the antipyretic activity of matrine, a Lupin alkaloid from Sophara subprostrata[J]. Planta Medica, 1980, 52: 343.
30.刘国卿,袁惠南,谢林等.槐果碱等苦豆子生物碱对大鼠单胺代谢及多巴胺和5-羟色胺受体的作用[J].药学学报, 1987, 22(9): 645-649.
31.余建强,蒋袁絮.槐定碱对小鼠中枢神经系统的影响[J].中草药, 2006, 37(11): 1688-1691.
32.余建强,蒋袁絮.槐定碱对大鼠中枢谷氨酸及氨基丁酸免疫阳性细胞的影响[J].中药药理与临床, 2006, 22(2): 17-19.
33.陆钊罡,牟青春,侯延辉,彭晓东.槐定碱致癫痫样作用研究[J].已投送《中国中药杂志》,待发表.
34.倪晶晶,吴仲敏,凌树才等.苦参碱注射液对老年痴呆模型大鼠脑组织白细胞介素1β含量及海马神经元超微结构的影响[J].解剖学杂志, 2006, 29(5): 608-611.
2. Abe K, Yamaguchi S, Sugiura M, Saito H. (1999) The ethanol metabolite acetaldehyde inhibits the induction of long-term potentiation in the rat dentate gyrus in vivo. Br J Pharmacol. 127(8):1805-1810.
3. Abraham WC, Gustafsson B, Wigstr?m H. (1987) Long-term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea-pig hippocampus. J Physiol. 394:367-380.
4. Albertson TE, Joy RM. (1987) Increased inhibition in dentate gyrus granule cells following exposure to GABA-uptake blockers. Brain Res. 435(1-2):283-292.
5. Andersen P, Bliss TV, Skrede KK. (1971) Unit analysis of hippocampal polulation spikes. Exp Brain Res. 13(2):208-221.
6. Bliss TVP, Collingridge GL. (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 361(6407): 31-39.
7. Bliss TV, Gardner-Medwin AR. (1973a) Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol. 232(2):357-374.
8. Bliss TV, Lomo T. (1973b) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 232(2):331-356.
9. Bramham CR, Milgram NW, Srebro B. (1991) Delta opioid receptor activation is required to induce LTP of synaptic transmission in the lateral perforant path in vivo. Brain Res. 567(1):42-50.
10. Bramham CR, Sarvey JM. (1996) Endogenous activation of mu and delta-1 opioid receptors is required for long-term potentiation induction in the lateral perforant path: dependence on GABAergic inhibition. J Neurosci. 16(24):8123-8131.
11. Burgard EC, Cote TE, Sarvey JM. (1993) Muscarinic depression of synaptic transmission and blockade of norepinephrine-induced long-lasting potentiation in the dentate gyrus. Neuroscience. 54(2):377-389.
12. Burwell RD, Witter MP, Amaral DG. (1995) Perirhinal and postrhinal cortices of the rat: a review of the neuroanatomical literature and comparison with findings from the monkey brain. Hippocampus. 5(5):390-408.
13. Charlton MP, Smith SJ, Zucker RS. (1982) Role of presynaptic calcium ions and channels in synaptic facilitation and depression at the squid giant synapse. J Physiol. 323:173-193.
14. Debanne D, Guérineau NC, G?hwiler BH, Thompson SM. (1996) Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release. J Physiol. 491 ( Pt 1):163-176.
15. Douglas RM, Goddard GV. (1975) Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus. Brain Res. 86(2):205-215.
16. Drake CT, Chavkin C, Milner TA. (2007) Opioid systems in the dentate gyrus. Prog Brain Res. 163:245-263.
17. Frotscher M, Léránth C. (1985) Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: a combined light and electron microscopic study. J Comp Neurol. 239(2):237-246.
18. Gaykema RP, Luiten PG, Nyakas C, Traber J. (1990) Cortical projection patterns of the medial septum-diagonal band complex. J Comp Neurol. 293(1):103-124.
19. Gilbert ME, Mack CM. (1999) Field potential recordings in dentate gyrus of anesthetized rats: stability of baseline. Hippocampus. 9(3):277-287.
20. Goodman LS et al. (1993) Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York, MacMillan, 213–214.
21. Halasy K, Somogyi P. (1993) Subdivisions in the multiple GABAergic innervation of granule cells in the dentate gyrus of the rat hippocampus. Eur J Neurosci. 5(5):411-429.
22. Hamid S, Dawe GS, Gray JA, Stephenson JD. (1997) Nicotine induces long-lasting potentiation in the dentate gyrus of nicotine-primed rats. Neurosci Res. 29(1):81-85.
23. Hessler NA, Shirke AM, Malinow R. (1993) The probability of transmitter release at a mammalian central synapse. Nature. 366(6455):569-572.
24. Higashiyama K, Takeuchi Y, Yamauchi T, Imai S, Kamei J, Yajima Y, et al. (2005) Implication of the descending dynorphinergic neuron projecting to the spinal cord in the (+)-matrine-and (+)-allomatrine-induced antinociceptive effects. Biol Pharm Bull. 28(5):845-848.
25. H?lscher C, Anwyl R, Rowan MJ. (1997) Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can Be depotentiated by stimulation on the negative phase in area CA1 in vivo. J Neurosci. 17(16):6470-6477.
26. H?lscher C. (1999) Synaptic plasticity and learning and memory: LTP and beyond. J Neurosci Res. 58(1):62-75.
27. Iga Y, Arisawa H, Ise M, Yasuda H, Takeshita Y. (1996) Modulation of rhythmical slow activity, long-term potentiation and memory by muscarinic receptor agonists. Eur J Pharmacol. 308(1):13-19.
28. Ikegaya Y, Saito H, Torii K, Nishiyama N. (1997) Activin selectively abolishes hippocampal long-term potentiation induced by weak tetanic stimulation in vivo. Jpn J Pharmacol. 75(1):87-89.
29. Joy RM, Albertson TE. (1993) NMDA receptors have a dominant role in population spike-paired pulse facilitation in the dentate gyrus of urethane-anesthetized rats. Brain Res. 604(1-2):273-282.
30. Kamei J, Xiao P, Ohsawa M, Kubo H, Higashiyama K, Takahashi H, Li J, Nagase H, Ohmiya S. (1997) Antinociceptive effects of (+)-matrine in mice. Eur J Pharmacol. 337(2-3):223-226.
31. Katz B, Miledi R. (1968) The role of calcium in neuromuscular facilitation. J Physiol. 195(2):481-492.
32. Korol DL, Gold PE. (2008) Epinephrine converts long-term potentiation from transient to durable form in awake rats. Hippocampus. 18(1):81-91.
33. Madison DV, Nicoll RA. (1988) Enkephalin hyperpolarizes interneurones in the rat hippocampus. J Physiol. 398:123-130.
34. McNaughton BL, Barnes CA. (1977) Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat. J Comp Neurol. 175(4):439-454.
35. Morris BJ, Johnston HM. (1995) A role for hippocampal opioids in long-term functional plasticity. Trends Neurosci. 18(8):350-355.
36. Moser EI. (1996) Altered inhibition of dentate granule cells during spatial learning in an exploration task. J Neurosci. 16(3):1247-1259.
37. Murthy VN, Sejnowski TJ, Stevens CF. (1997) Heterogeneous release properties of visualized individual hippocampal synapses. Neuron. 18(4):599-612.
38. Nadim F, Manor Y. (2000) The role of short-term synaptic dynamics in motor control. Curr Opin Neurobiol. 10(6):683-690.
39. Pang K, Williams MJ, Olton DS. (1993) Activation of the medial septal area attenuates LTP of the lateral perforant path and enhances heterosynaptic LTD of the medial perforant path in aged rats. Brain Res. 632(1-2):150-160.
40. Paxinos G and Watson C. The Rat Brain in Stereotaxic Coordinates. Academic press Australia (Second Edition 1986) and Academic press USA (Compact Third Edition 1997).
41. Racine RJ. (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 32(3):281-294.
42. Rose G, Diamond D, Lynch GS. (1983) Dentate granule cells in the rat hippocampal formation have the behavioral characteristics of theta neurons. Brain Res. 266(1):29-37.
43. Simmons ML, Terman GW, Drake CT, Chavkin C. (1994) Inhibition of glutamate release by presynaptic kappa 1-opioid receptors in the guinea pig dentate gyrus. J Neurophysiol. 72(4):1697-1705.
44. Squire LR, Stark CE, Clark RE. (2004) The medial temporal lobe. Annu Rev Neurosci. 27:279-306.
45. Straube T, Korz V, Balschun D, Frey JU. (2003) Requirement of beta-adrenergic receptor activation and protein synthesis for LTP-reinforcement by novelty in rat dentate gyrus. J Physiol. 552(Pt 3):953-60.
46. Taube JS, Schwartzkroin PA. (1988) Mechanisms of long-term potentiation: EPSP/spike dissociation, intradendritic recordings, and glutamate sensitivity. J Neurosci. 8(5):1632-1644.
47. Terman GW, Drake CT, Simmons ML, Milner TA, Chavkin C. (2000) Opioid modulation of recurrent excitation in the hippocampal dentate gyrus. J Neurosci. 20(12):4379-4388.
48. Terman GW, Wagner JJ, Chavkin C. (1994) Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus. J Neurosci. 14(8):4740-4747.
49. Thalmann RH, Ayala GF. (1982) A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus. Neurosci Lett. 29(3):243-248.
50. Tsodyks MV, Markram H. (1997) The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proc Natl Acad Sci U S A. 94(2):719-723.
51. Wagner JJ, Caudle RM, Chavkin C. (1992) Kappa-opioids decrease excitatory transmission in the dentate gyrus of the guinea pig hippocampus. J Neurosci. 12(1):132-141.
52. Wagner JJ, Terman GW, Chavkin C. (1993) Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus. Nature. 363(6428):451-454.
53. Williams S, Johnston D. (1988) Muscarinic depression of long-term potentiation in CA3 hippocampal neurons. Science. 242(4875):84-7.
54. Winson J, Dahl D. (1986) Long-term potentiation in dentate gyrus: induction by asynchronous volleys in separate afferents. Science. 234(4779):985-988.
55. Witter MP. (2007) The perforant path: projections from the entorhinal cortex to the dentate gyrus. Prog Brain Res. 163:43-61.
56. Yanagihashi R, Ishikawa T. (1992) Studies on long-term potentiation of the population spike component of hippocampal field potential by the tetanic stimulation of the perforant path rats: effects of a dopamine agonist, SKF-38393. Brain Res. 579(1):79-86.
57. Yin LL, Zhu XZ. (2005) The involvement of central cholinergic system in (+)-matrine-induced antinociception in mice. Pharmacol Biochem Behav. 80(3):419-425.
58. Zieglg?nsberger W, French ED, Siggins GR, Bloom FE. (1979) Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurons. Science. 205(4404):415-417.
59. Zucker RS. (1989) Short-term synaptic plasticity. Annu Rev Neurosci. 12:13-31.
60. Zucker RS. (1999) Calcium- and activity-dependent synaptic plasticity. Curr Opin Neurobiol. 9(3):305-313.
61.钟仁山,苦豆子的研究及其应用.第1版[M].银川:宁夏人民出版社, 1983:165
62.袁惠南,何汉增,尹玉琴等.苦参碱的中枢药理作用[J].浙江药学, 1986, 3(6):5-9
63.王绪平,陈庆梅,郑筱祥.苦参醇提取液镇静催眠作用的实验研究[J].中草药, 2004,35(5):551-553
64.王绪平,陈继平,章建民等.苦参碱对海马神经中枢抑制作用的研究[J].浙江中医杂志, 2007, 42(9):539-541
65.耿群美,李兰诚,贾晓英.苦参碱、氧化苦参碱对小鼠脑中递质γ-氨基丁酸和甘氨酸含量的影响[J].内蒙古医学院学报, 1992, 14(1):8-9
66.王秀坤,李家实.苦参碱等槐属六种生物碱对GABAA受体的作用[J].北京中医药大学学报, 2000, 23(supp):42-43
67.李玉香,白洁.槐定碱对大鼠皮层脑电的影响[J].中药药理与临床, 2007, 23(1):24-26.
68.胡淑婷,奥海航,陈晓霞等.槐定碱致痫大鼠模型的建立及血清TNF-α和IL-1β含量变化的研究[J].宁夏医学杂志, 2008, 30(12): 1065-1068
69.韩太真,突触可塑性与长时程增强现象的研究进展[J].西安交通大学学报(医学版), 2005, 26(4):305-308
70.贾凡,周逸峰.短时程突触可塑性的功能意义[J].生物化学与生物物理进展, 2000, 27(2): 174-177
71.许绍芬.神经生物学[M].上海:上海医科大学出版社, 1990: 262-268
72.梅镇彤.学习和记忆的神经生物学[M].上海:上海科技教育出版社, 1997:38-44
73.李雪梅,庄文华,姜鸷滋等.高剂量槐定碱对大鼠神经系统长期毒性的病理形态学观察[J].癌症, 2004, 23(11s): 1376-1378
74.陈晓霞,胡淑婷,杨雪琴等.槐定碱致痫大鼠海马Glu、GABA及血清中TNF、IL-2和IL-6含量变化的研究[J].宁夏医学院学报, 2007, 29(5): 944-945
75.彭晓东,许大庆,彭建中等.枸杞多糖对动物海马电活动的影响[J].宁夏医学院学报, 2002, 24(2): 79-81
76.肖培根.新编中药志(第一卷)[M].北京:化学工业出版社, 2002: 560
77.张晓丹,李显庆,邵碧霞,马灵芝.苦参碱的药代动力学及心血管作用研究进展[J].时针国医国药, 2006, 17(12): 2605-2606
78.王平全,陈曙霞,周贤飙,李丹,陆国红,陈美芳.苦参碱在大鼠体内的药物动力学[J].上海第二医科大学学报, 1996, 16(4): 250-252
79.庞志功,汪宝琪,王翔.口服苦参碱的药代动力学研究[J].西安医科大学学报, 1998, 19(2): 201
80.张守芳.中草药通讯[J]. 1977, 2: 39-41
81.黄圣凯,陈静芬,谢永新,袁惠南.槐定碱的气相色谱测定法及其在兔体内的药代动力学[J].药学学报, 1988, 23(8): 561-565
82.胡一中,黄圣凯.槐定碱的生理药动学模型[J].中国药理学与毒理学杂志, 1995, 9(2): 133-136
83.温玉麟.药物与化学物质毒性数据. [M].天津:天津科学技术出版社, 1989: 44
84.彭晓东,闫乾顺,闫琳等.鹅绒藤对小鼠抗惊厥作用的观察[J].第四军医大学学报, 2009, 30(4): 340-343
85.韩丹,张先荣,唐岳枫等.强直电刺激大鼠海马、中部颞叶新皮质诱发癫癇模型中电振荡与癫癇发生的关系研究[J].中国神经科学杂志, 2000, 16(2): 108-114
86.李雪梅,吴运光,潘达鑫等.新型抗肿瘤药槐定碱[J].中国新药杂志, 2006, 15(8): 654-657
87.余建强,蒋袁絮.槐定碱对大鼠中枢谷氨酸及氨基丁酸免疫阳性细胞的影响[J].中药药理与临床, 2006a, 22(2): 17-19
88.余建强,蒋袁絮.槐定碱对小鼠中枢神经系统的影响[J].中草药, 2006b, 37(11): 8861-8863
1.国家医药管理局中草药情报中心站编.植物药有效成分手册[M].北京,人民卫生出版社, 1985: 700.
2.刘梅,刘雪英,程建峰.苦参碱的药理研究[J].中国中药杂志, 2003, 28(9): 801-804.
3.钟仁山主编.苦豆子的研究及其应用[M].宁夏人民出版社, 1983出版.
4.袁惠南,何汉增,赵雅灵等.槐果碱对中枢神经系统的抑制作用[J].中药通报, 1987, 12(4): 45-47.
5.袁惠南,何汉增,尹玉琴等.苦参碱的中枢药理作用[J].浙江药学, 1986, 3(6): 5-9.
6.袁惠南,何汉增,赵雅灵等.槐胺碱对中枢神经系统的影响[J].西北药学杂志, 1986, 1(4): 12-14.
7.蒋袁絮,余建强,彭建中.氧化苦参碱对小鼠的中枢抑制作用[J].宁夏医学院学报, 2000, 22(3): 157-158.
8.余建强,蒋袁絮,彭建中.氧化槐定碱对小鼠中枢的抑制作用[J].华西药学杂志, 2001, 16(4): 277-278.
9.余建强,蒋袁絮,王丽韫.氧化槐定碱和氧化苦参碱对小鼠中枢的抑制作用[J].宁夏医学杂志, 2002, 24(1): 13-15.
10.耿群美,李兰诚,贾晓英.苦参碱、氧化苦参碱对小鼠脑中递质γ-氨基丁酸和甘氨酸含量的影响[J].内蒙古医学院学报, 1992, 14(1): 8-9.
11.王绪平,陈继平,章建民,陆建荣,洪学智.苦参碱注射液对小鼠脑海马氨基酸神经递质的作用研究[J].中成药, 2008, 30(8): 1218-1219.
12.王秀坤,李家实.苦参碱等槐属六种生物碱对GABAA受体的作用[J].北京中医药大学学报, 2000, 23(supp): 42-43.
13.王绪平,陈庆梅,郑筱祥.苦参醇提取液镇静催眠作用的实验研究[J].中草药, 2004, 35(5): 551-553.
14.陈庆梅,王绪平,张恒义,郑筱祥.群峰电位的定量分析及其在苦参碱研究中的应用[J].航天医学与医学工程, 2004, 17(4): 303-305.
15.王绪平,陈继平,章建民,陆建荣.苦参碱对海马神经中枢抑制作用的研究[J].浙江中医杂志, 2007, 42(9): 539-541.
16.罗学娅,张学梅,高卫,吴琴芳.苦参碱的镇痛作用部位及机制研究[J].中草药, 2001, 32(1): 41-43.
17.王百忍,赵经纬.一氧化氮与疼痛[J].神经解剖学杂志, 1995, 11(1): 69-74.
18.黄秀梅,李波.六种苦豆子生物碱对炎症介质白三烯的影响[J].中成药, 2003, 25(10): 8242-8261.
19. Kamei J, Xiao P, Ohsawa M, Kubo H, Higashiyama K, Takahashi H, et al. Antinociceptive effects of (+)-matrine in mice[J]. Eur J Pharmacol 1997; 337: 223-226.
20. Higashiyama K, Takeuchi Y, Yamauchi T, Imai S, Kamei J, Yajima Y, et al. Implication of the descending dynorphinergic neuron projecting to the spinal cord in the (+)-matrine-and (+)-allomatrine-induced antinociceptive effects[J]. Biol Pharm Bull 2005; 28(5): 845-848.
21. Lin-lin Yin, Xing-zu Zhu. The involvement of central cholinergic system in (+)-matrine-induced antinociception in mice[J]. Pharmacology, Biochemistry and Behavior 80 (2005): 419-425.
22.陈霞,刘芬,吕文伟等.氧化苦参碱的镇痛作用及其机制研究[J].中草药, 2006, 37(2): 255-257.
23.刘芬,刘洁,陈霞等.氧化苦参碱的镇痛作用及其机制[J].吉林大学学报(医学版), 2005, 31(6): 883-885.
24. Kobashi S, Kubo H, Yamauchi T, Higashiyama K. Antinociceptive effects of 1-acyl-4-dialkylaminopiperidine and 1-alkyl-4-dialkylaminopiperidine in mice: structure-activity relation study of matrine-type alkaloids[J]. Biol Pharm Bull 2002; 25(8): 1030-1034.
25.蔡本志,王玲,李春莉等.氧化苦参碱对大鼠海马神经元细胞钠通道的影响[J].哈尔滨医科大学学报, 2007, 41(2): 85-88.
26.张琳娜,白洁,刘红梅.氧化苦参碱对青霉素致痫大鼠的实验性研究[J].陕西中医, 2007, 28(6): 755-757.
27.胡淑婷,张志宁,陈晓霞,白洁.氧化苦参碱对青霉素致痫大鼠海马GABA、Glu及血清中细胞因子的影响[J].宁夏医学院学报, 2008, 30(6): 706-709.
28.白洁,张琳娜,胡淑婷,刘红梅.氧化苦参碱和槐定碱对青霉素致痫大鼠海马的影响[J].宁夏医学院学报, 2006, 28(6): 476-479.
29. Cho CH, Chuang CY, Chen CF. Study of the antipyretic activity of matrine, a Lupin alkaloid from Sophara subprostrata[J]. Planta Medica, 1980, 52: 343.
30.刘国卿,袁惠南,谢林等.槐果碱等苦豆子生物碱对大鼠单胺代谢及多巴胺和5-羟色胺受体的作用[J].药学学报, 1987, 22(9): 645-649.
31.余建强,蒋袁絮.槐定碱对小鼠中枢神经系统的影响[J].中草药, 2006, 37(11): 1688-1691.
32.余建强,蒋袁絮.槐定碱对大鼠中枢谷氨酸及氨基丁酸免疫阳性细胞的影响[J].中药药理与临床, 2006, 22(2): 17-19.
33.陆钊罡,牟青春,侯延辉,彭晓东.槐定碱致癫痫样作用研究[J].已投送《中国中药杂志》,待发表.
34.倪晶晶,吴仲敏,凌树才等.苦参碱注射液对老年痴呆模型大鼠脑组织白细胞介素1β含量及海马神经元超微结构的影响[J].解剖学杂志, 2006, 29(5): 608-611.