交泰丸干预对氯苯丙氨酸致大鼠失眠的代谢组学研究

Intervention effects of Jiaotai pills on PCPA-induced insomnia in rats

为了阐明交泰丸干预对氯苯丙氨酸(p-chlorophenylalanine,PCPA)致大鼠失眠的药效及作用机制,SD大鼠一次性腹腔注射PCPA建立失眠模型,试验期间观察大鼠自发活动变化,用酶联免疫吸附法(ELISA)检测大鼠下丘脑、海马、前额叶皮质和血清神经生长因子(nerve growth factor,NGF)水平,并利用核磁共振氢谱(1H-NM R)代谢组学技术建立大鼠血清及海马组织代谢物谱,分析交泰丸干预下大鼠自发活动,NGF水平及与失眠相关潜在生物标志物的变化。结果显示交泰丸能明显抑制失眠大鼠的自发活动,显著升高失眠大鼠下丘脑、海马、前额叶皮质和血清中NGF水平。交泰丸能对失眠所致大鼠血清和海马组织代谢紊乱产生有效的干预,并分别对血清和海马组织中6种和5种与失眠相关潜在生物标志物产生显著的回调。研究表明交泰丸干预PCPA所致失眠的机制可能与调节NGF水平及调控机体氨基酸代谢、脂质代谢和胆碱代谢有关。

To elucidate the intervention effects of Jiaotai pills （JTP） on p-chlorophenylalanine （PCPA）-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor（NGF） in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance（ 1H-NMR） -based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be inter- vened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by admin- istration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline.