Objective: To evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HT1AR) in the hippocampus in a rat model of insomnia.
Methods: Male KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HT1AR protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively.
Results: In the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (P<0.05); in the test with a threshold dose of sodium pentobarbital, treatment with moderate- and high-dose FSNSD resulted in significantly prolonged sleeping time (P<0.01) and shortened sleep latency (P<0.05) in the mice. The rats in insomnia model group showed increased total distance in open field test (P<0.05) with significantly decreased content of 5-HT (P<0.01) and expressions of 5-HT1AR protein and mRNA in the hippocampus (P<0.01). Treatment of the rats with estazolam or high-dose FSNSD obviously decreased the total distance in open field test (P<0.05) and increased the content of 5-HT (P<0.05) and expressions of 5-HT1AR (P<0.01) in the hippocampus of rats with insomnia.
Conclusion: FSNSD can produce therapeutic effects on insomnia possibly by increasing 5-HT content and expressions of 5-HT1AR in the hippocampus.
目的: 评价佛手宁神方镇静催眠作用并研究其对失眠大鼠海马5-羟色胺（5-HT）、5-羟色胺1A受体（5-HT1AR）表达的影响。
方法: 雄性昆明小鼠随机分为空白组，艾司唑仑组[0.4 mg/（kg·d）]，佛手宁神方低、中、高剂量组[12，24，48 g/（kg·d）]；连续给药1周，末次给药后进行阈下剂量和阈剂量戊巴比妥钠致小鼠睡眠实验。雄性SD大鼠随机分为空白组，模型组，艾司唑仑组[0.2 mg/（kg·d）]，佛手宁神方低、中、高剂量组[6，12，24 g/（kg·d）]，每组8只；采用腹腔注射对氯苯丙氨酸（PCPA）350 mg/（kg·d）制作失眠大鼠模型；造模完成后第1天开始灌胃给药，连续1周。旷场实验测试各组大鼠运动总路程和站立次数；酶联免疫吸附法测定海马5-HT的含量；免疫组化法和实时荧光定量PCR分别检测海马5-HT1AR蛋白和mRNA的表达。
结果: 与空白组相比，佛手宁神方高剂量组阈下剂量戊巴比妥钠致小鼠入睡只数增加（P＜0.05），阈剂量戊巴比妥钠致小鼠睡眠潜伏期缩短（P＜0.01），睡眠持续时间延长（P＜0.01）。与空白组比较，模型组大鼠在旷场实验中运动总路程增加（P＜0.05），海马5-HT含量减少（P＜0.01），海马5-HT1AR蛋白和mRNA表达水平下降（P＜0.01）。与模型组相比，艾司唑仑组和佛手宁神方高剂量组运功总路程减少（P＜0.05），海马5-HT含量增加（P＜0.05），海马5-HT1AR蛋白和mRNA表达水平上升（P＜0.01）。
结论: 佛手宁神方可能通过提高海马5-HT的含量，上调海马5-HT1AR蛋白和mRNA的表达，从而起到治疗失眠的作用