百乐眠胶囊对失眠症小鼠的治疗机制

Mechanism of Bailemian capsules in the treatment of insomnia in mice

目的探讨百乐眠胶囊对失眠症小鼠的治疗机制。方法ICR小鼠50只，按随机平行对照法分为正常对照组、模型组、百乐眠胶囊低、中、高剂量组共5组。百乐眠胶囊3个剂量组预防性灌胃给药14d后，除正常对照组外，其余各组均腹腔注射对氯苯丙氨酸（PCPA），建立失眠小鼠模型，造模后观察各组小鼠一般行为学并检测其脑组织中5-羟色胺（5-HT）和^γ氨基丁酸（GABA）含量。另外两批ICR小鼠各50只，分别按随机平行对照法分为正常对照组、安定组、百乐眠胶囊低、中、高剂量组共5组，实验前禁食14h，除正常对照组外分别进行安定或百乐眠灌胃给药；一批观察给药前及给药后30、60、120、240min小鼠的一般行为，记录其5min内活动次数；另一批给药30min后，腹腔注射戊巴比妥钠25mg／kg，以翻正反射消失为睡眠指标，观察小鼠15min入睡比例、睡眠潜伏期和总睡眠时间。结果百乐眠胶囊中、高剂量组小鼠失眠症状显著改善，其脑组织中的5-HT和GABA含量均显著高于模型组[（164．6±12．8）、（193．2±25．6）比（147．1±15．5）ng／ml和（15．4±1．3）、（17．0±1．3）比（12．6±1．4）I．zmol／L]（均P〈0．05），且给药后120min小鼠活动次数显著少于正常对照组[（91．3±10．4）、（78．5±12．7）比（150．7±10．8）次]（均P〈0．05）。百乐眠低、中、高剂量均可提高小鼠15min入睡比例，其睡眠潜伏期均短于正常对照组[（8．9±0．6）、（7．34-0．6）、（2．1±0．3）比0min）]，总睡眠时间均长于正常对照组[（76．7±7．1）、（85．1±7．1）、（110．0±22．9）比0min）]（均P〈0．05）。结论百乐眠胶囊可以通过提高脑内5-HT和GABA含量来治疗失眠症。

Objective To explore the mechanism of Bailemian capsules in the treatment of insomnia. Methods A total of 50 imprinting control region （ICR） mice were randomly divided into 5 groups of normal control, model, high, medium and low-dose Bailemian capsules. After oral administration of Bailemian capsules for 14 consecutive days, except for control group, the other four groups received an injection of chlorobenzene alanine （PCPA） for murine modeling of insomnia. Then murine behaviors were observed and the brain tissue levels of serotonin （5-HT） and γ-aminobutyric acid （GABA） were detected. Another two batches of ICR mice （ n = 50 each） were randomly divided into 5 groups of normal control, diazepam, high, medium and low-dose Bailemian capsules. After 14-hour fasting, except for normal control group, an intragastric dose of Bailemian was offered. Before dosing and at 30, 60, 120, 240 min, general behaviors within 5 min were recorded. For another batch, at 30 min after an intraperitoneal injection of pentobarbital sodium 25 mg/kg, disappearance of righting reflex as sleep index was used to observe the proportion of mice within 15 min in terms of sleep, sleep latency and total sleep time. Results In middle and high-dose groups, insomnia symptoms improved significantly. The contents of 5-HT and GABA in brain tissue were significantly higher than those of model group （ （ 164. 6 ± 12. 8）, （ 193.2±25.6） vs （ 147.1 ± 15.5） ng/ml and （ 15.4 ±1.3）, （ 17. 0 ± 1.3） vs （ 12. 6± 1.4） mol/L） （all P 〈0. 05）. And the number of activities at 120 min was significantly less than that of normal control group （ （91.3 ~ 10. 4）, （78.5 ＋ 12. 7） vs （150. 7 ±10. 8） times） （both P〈O. 05）. Low, medium and high-dose Bailemian capsules could improve the proportion of mice within 15 min sleep. And sleep latency was shorter than that of normal control group （ （ 8.9± 0. 6 ）, （7. 3 ± 0. 6 ）, （ 2. 1 ± 0. 3 ） vs 0 min） and total sleep time longer than that of normal control group （ （76. 7 ± 7.1 ）, （ 85.1 ±7. 1 ）, （ 110. 0 ±22. 9 ） vs 0 min） （ all P 〈 0.05 ）. Conclusion The mechanism of Bailemian capsules for treating the symptoms of insomnia may be related with the elevated brain contents of 5-HT and GABA.