枢机安神汤对氯苯丙氨酸失眠大鼠神经递质和焦虑的影响

Effects of Shuji Anshen Decoction on Neurotransmitters and Anxiety in p-Chlorophenylalanine-induced Insomnia Rats

目的:研究枢机安神汤对氯苯丙氨酸(PCPA)失眠大鼠神经递质和焦虑的影响。方法:将大鼠分为对照组、模型组、中药低剂量组(8.5 g/kg)、中药中剂量组(13 g/kg)、中药高剂量组(17 g/kg)以及西药组(0.26 mg/kg),在建模后各组大鼠连续给药7 d,采用苏木精-伊红(HE)染色法观察大鼠海马组织病理改变,酶联免疫吸附试验(ELISA)检测各组大鼠海马组织中5-羟吲哚乙酸(5-HIAA)、5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)和血清中褪黑素(MT)的含量,蛋白质印迹法(Western Blotting)检测大鼠海马组织中乙酰胆碱酯酶(AChE)、脑源性神经营养因子(BDNF)的蛋白表达含量。结果:成功建立大鼠失眠模型,枢机安神汤能够提高大鼠体质量和睡眠时间,增加大鼠海马CA1区锥体细胞数量,增加海马组织中5-HIAA、5-HT、AChE、BDNF与血清中MT的含量,抑制海马组织中NE、DA含量。结论:枢机安神汤可改善PCPA失眠大鼠神经递质和焦虑状态,其机制与增加5-HT含量有关。另外,枢机安神汤还通过激活前额叶突触可塑性标志蛋白BDNF的表达,改善PCPA失眠大鼠的学习记忆能力。

Objective:To study the effect of Shuji Anshen Decoction on neurotransmitters and anxiety in p-chlorophenylalanine(PCPA)-induced insomnia rats.Methods:The rats were divided into control group,model group,low-dose Chinese medicine group(8.5 g/kg),medium-dose Chinese medicine group(13 g/kg),high-dose Chinese medicine group(17 g/kg) and western medicine group(0.26 mg/kg).After modeling,the rats in each group were continuously administered for 7 days.Hematoxylin-eosin(HE) staining was used to observe the pathological changes of hippocampus.Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of 5-hydroxyindoleacetic acid(5-HIAA),serotonin(5-HT),norepinephrine(NE),dopamine(DA) and melatonin(MT) in hippocampus.Western blotting was used to detect the protein expression of acetylcholinesterase(AChE) and brain-derived neurotrophic factor(BDNF) in hippocampus.Results:The rat model of insomnia was successfully established.Shuji Anshen Decoction could increase the body weight and sleep time,increase the number of pyramidal cells in CA1 region of hippocampus,increase the contents of 5-HIAA,5-HT,AChE,BDNF in hippocampus and MT in serum,and reduce the contents of NE and DA in hippocampus.Conclusion:Shuji Anshen Decoction could improve neurotransmitter and anxiety in PCPA-induced insomnia rats,and the mechanism was related to the increase of 5-HT content.In addition,Shuji Anshen Decoction also improved the learning and memory ability of PCPA-induced insomnia rats by activating the protein expression of BDNF,a marker protein of synaptic plasticity in the prefrontal cortex.