茯神宁神汤通过5-羟色胺能系统改善失眠大鼠模型的睡眠
[Foshouningshen decoction improves sleeping via the serotonergic system in a rat model of insomnia].
作者信息
Huang Jie-Cong, Xie Wei, Deng Ning, Liang Wen-Lin, Hu Dong-Rong, Hong Yu, Zhou Yang
机构信息
College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. E-mail:
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2017 Aug 20;37(8):1116-1120. doi: 10.3969/j.issn.1673-4254.2017.08.19.
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-HTR) 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-HTR 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-HTR 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-HTR (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-HTR in the hippocampus.
目的
评价茯神宁神汤（FSNSD）的镇静催眠作用，并研究其对失眠大鼠模型海马中5-羟色胺（5-HT）及5-HT1A受体（5-HTR）表达的影响。
方法
将雄性KM小鼠分为对照组、艾司唑仑（每日0.4mg/kg）组、FSNSD低、中、高剂量组（每日剂量分别为12、24、48g/kg）。相应处理1周后，小鼠分别给予阈下剂量和阈剂量戊巴比妥钠进行诱眠试验。将48只雄性SD大鼠随机分为对照组、失眠模型组、艾司唑仑组（每日0.2mg/kg）、FSNSD低、中、高剂量组（每日剂量分别为6、12、24g/kg）。通过腹腔注射350mg/kg的4-氯-dl-苯丙氨酸（PCPA），连续3天建立大鼠失眠模型，之后大鼠通过灌胃接受相应处理1周。记录大鼠在旷场试验中的表现，采用ELISA法检测海马中5-HT的表达；分别采用免疫组化和实时荧光定量PCR法检测海马中5-HTR蛋白和mRNA的表达。
结果
在阈下剂量戊巴比妥钠诱眠试验中，高剂量FSNSD处理的小鼠入睡率显著高于对照小鼠（P<0.05）；在阈剂量戊巴比妥钠试验中，中、高剂量FSNSD处理使小鼠睡眠时间显著延长（P<0.01），睡眠潜伏期缩短（P<0.05）。失眠模型组大鼠旷场试验总路程增加（P<0.05），海马中5-HT含量显著降低（P<0.01），5-HTR蛋白和mRNA表达显著降低（P<0.01）。给予艾司唑仑或高剂量FSNSD处理可使失眠大鼠旷场试验总路程明显减少（P<0.05），海马中5-HT含量增加（P<0.05），5-HTR表达增加（P<0.01）。
结论
FSNSD可能通过增加海马中5-HT含量及5-HTR表达而对失眠产生治疗作用。
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