氧化苦参碱的中枢抑制和神经保护作用研究进展

Research advance on central suppression and neuroprotection of oxymatrine

氧化苦参碱具有镇静、催眠、降体温、抗癫痫、改善认知功能、保护脑神经和外周神经作用。其作用机制可能是激活大麻素2型受体和上调电压门控钙离子N型通道表达,促进抑制性神经递质(γ-氨基丁酸、甘氨酸)合成与释放,下调γ-氨基丁酸转运体-1表达,使突触间隙γ-氨基丁酸浓度升高以及上调γ-氨基丁酸-A受体表达,从而增强γ-氨基丁酸能神经功能。γ-氨基丁酸能神经功能的增强可抑制兴奋性神经递质谷氨酸过度表达并下调N-甲基-D-天冬氨酸(NMDA)受体和蛋白激酶Cγ表达,从而下调电压门控钙离子L型通道的表达,抑制钙离子内流,阻滞钙/钙调素依赖性蛋白激酶Ⅱ/c-AMP反应元件结合蛋白通路,抑制炎症反应,产生中枢抑制和神经保护作用。

Oxymatrine has the effects of sedation, hypnotism, hypothermia, anti-epilepsy, enhancing cognitive function and neuroprotective effect to peripheral nerve, and cranial nerves injury. The active mechanism of oxymatrine may can activate cannabine receptor-2 and up-regulate the expression of N-type voltage-gated calcium channels, improve synthesis and release of inhibitory neurotransmitters, γ-aminobutyric acid (GABA) and glycine, down-regulate the expression of GABA transporter 1 (GAT- 1), increase the concentration of GABA in synaptic cleft, and up-regulate the expression of GABAA receptor, thus strengthen GABAergic nerve function. Enhancement of GABAergic nerve function can inhibit the expression of excitatory neurotransmitter, glutamic acid, N-methyl-D-aspartate (NMDA) receptor, and protein kinase Cγ, thus down-regulate the expression of L-type voltagegated calcium channels, and inhibit Ca2+ influent, and blocking CaMKⅡ/CREB pathway to inhibit inflammation and product central suppression and neuroprotection.