槟榔次碱速效抗疲劳活性及其通过调控血脑屏障发挥抗疲劳机制研究

Study on the quick-acting antifatigue activity of arecaidine and its mechanism of anti-fatigue by regulating the blood brain barrier

为探索槟榔次碱抗疲劳产品的开发前景,通过构建小鼠行为敏化模型,采用力竭游泳时间、血乳酸、血红蛋白(Hb)、血尿素氮、丙二醛、肌糖原、肝糖原、伊文思蓝、5-羟色胺(5-hydroxytryptamine, 5-HT)、多巴胺(Dopamine, DA)和5-HT/DA值等指标分析槟榔次碱速效抗疲劳活性及机制.结果显示,槟榔次碱能延长小鼠力竭游泳时间,且行为敏化可有效增强槟榔次碱的活性,2组行为敏化小鼠的力竭游泳时间均极显著大于2个未敏化处理及2个对照(P<0.01),口腔缓释给药对槟榔次碱处理小鼠的力竭游泳时间也有促进作用.槟榔次碱可抑制游泳小鼠血乳酸、丙二醛和血尿素氮的积累,缓解Hb和DA水平的降低,减弱脑内5-HT的升高,抑制肌糖原和肝糖原的耗竭,阻碍脑内5-HT/DA值的升高,增强血脑屏障(Blood-Brain Barrier, BBB)的通透性,且行为敏化和口腔缓释给药能增强上述效果.槟榔次碱可通过抑制氧运输蛋白水平降低、平衡中枢神经递质、降低代谢产物积累和能量物质消耗,并调节BBB通透性使脑内5-HT扩散到血液中,降低5-HT对大脑兴奋的抑制,从而发挥抗疲劳作用.槟榔次碱只有通过口腔缓释给药才能对行为敏化的机体挥卓越的速效抗疲劳活性,速效抗疲劳的原因可能是槟榔次碱通过口腔黏膜吸收,避免肠胃的首过效应,迅速增加进入血液循环系统.该研究可为槟榔次碱速效抗疲劳产品研发提供理论支撑.

To explore the development prospects of arecaidine anti fatigue products,a mouse behavioral sensitization model was constructed to analyze the quick-acting anti fatigue activity and its mechanism of arecaidine by using indicators such as the exhaustive swimming time,blood lactate,hemoglobin(Hb),blood urea nitrogen,malondialdehyde,muscle glycogen,liver glycogen,Evans blue,5-hydroxytryptamine(5-HT),dopamine(DA)and 5-HT/DA value.The results showed that arecaidine could prolong the exhaustive swimming time of mice,and behavioral sensitization could effectively enhance the activity of arecaidine.The exhaustive swimming time of both treatments of behavioral sensitized mice was significantly longer than that of two non sensitized treatments and two controls(P<0.01).Oral sustained-release administration also promoted the activity of arecaidine.Arecaidine can inhibit the accumulation of blood lactate,malondialdehyde and blood urea nitrogen in swimming mice,and alleviate the decrease in Hb and DA levels,and weaken the increase of 5-HT in the brain,and inhibit the depletion of muscle glycogen and liver glycogen,and hinder the increase of 5-HT/DA values in the brain,and enhance the permeability of the blood-brain barrier(BBB),Moreover,and behavioral sensitization and oral sustained-release administration can enhance the above effects.Arecaidine can exert anti fatigue effects by inhibiting the decrease of oxygen transport protein levels,balancing central neurotransmitters,reducing the accumulation of metabolites and energy consumption,regulating BBB permeability to allow 5-HT in the brain to diffuse into the bloodstream,and reducing the inhibition of 5-HT on brain excitation.Arecaidine can only exert excellent quick-acting anti fatigue activity on behavior sensitized organisms through oral sustained-release administration,the reason may be that arecaidine is absorbed through the oral mucosa,avoiding the first pass effect of the gastrointestinal tract and rapidly increasing its entry into the bloodstream.This study can provide theoretical support for the development of quick-acting anti fatigue products of arecaidine.