复方薰衣草颗粒镇静催眠及改善认知障碍作用研究

目的 观察复方薰衣草颗粒（CLG）镇静催眠及对轻度认知功能障碍（MCI）模型小鼠的治疗作用。方法 （1）CLG镇静催眠和抗抑郁、抗疲劳作用研究：以旷场训练结果为主要条件、体质量为次要条件,随机将79只ICR小鼠分为对照组、地西泮（3 mg·kg^-1,化药阳性药）组、复方枣仁胶囊（12.3 mg·kg^-1,中药阳性药）组和CLG低、中、高剂量（2.36、4.72、9.44 g·kg^-1）组。采用戊巴比妥钠阈下剂量催眠、旷场和转棒实验,观察CLG对小鼠的一般状态、睡眠潜伏期、30 min内入睡比例和总睡眠时间以及行为学的影响。（2）CLG改善MCI作用研究：将60只昆明小鼠以Y迷宫实验训练结果为主要条件、体质量为次要条件随机分为对照组、模型组、多奈哌齐（3 mg·kg^-1,阳性药）组和CLG低、中、高剂量（2.36、4.72、9.44 g·kg^-1）组,每天1次,连续ig给药14 d,给药第9天起,给药1 h后,除对照组外,ip 3 mg·kg^-1东莨菪碱制备MCI模型。于末次给药20 min后进行Y迷宫实验;第15天进行跳台实验;解剖取脑,称取脑质量并计算脑系数;HE染色后观察脑组织病理改变;取海马,ELISA法测定乙酰胆碱（Ach）、乙酰胆碱酯酶（AchE）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）水平。结果 （1）与对照组比较,CLG各剂量对体质量无明显影响;地西泮组和CLG各剂量组入睡率有增高趋势,但无显著性差异;地西泮组和CLG高剂量组入睡潜伏期明显缩短（P<0.05） ;各给药组睡眠时间均显著延长（P<0.01）。（2）与模型组比较,多奈哌齐组和CLG各剂量组跳台次数均显著减少（P<0.05）;CLG各剂量组Ach有升高趋势,多奈哌齐组和CLG中、高剂量组AchE有降低趋势;CLG各剂量组SOD显著增加,MDA显著降低（P<0.05）;CLG中、高剂量组小鼠皮层和海马病理改变明显减轻。结论 CLG具有镇静催眠作用,其改善MCI的作用可能与调节胆碱能系统和抗氧化应激有关。

Study of sedative and hypnotic effects of Compound Lavender Granule and its effect on cognitive impairment

Objective To observe the sedative and hypnotic effects of Compound Lavender Granule (CLG) and its effect on mild cognitive impairment (MCI) model mice. Methods (1) Studies on the sedative and hypnotic effects and anti-depression and antifatigue effects of CLG:Taking open field training results as the main condition and body weight as the secondary condition, 79 ICR mice were randomly divided into control group, diazepam (chemical positive drug, 3 mg·kg^-1) group, FuFang ZaoRen JiaoNang (Chinese traditional positive drug,12.3 mg·kg^-1) group, and CLG low, medium, and high dose (2.36, 4.72, and 9.44 g·kg^-1) group. The effects of CLG on general state, sleep latency, proportion of falling asleep within 30 min, total sleep time and behavior of mice were observed by using pentobarbital sodium subthreshold dose hypnosis test, open field test and rotating bar test. (2) Effect of CLG on MCI:60 KM mice were divided into six groups:control group, model group, donepezil (3 mg·kg^-1, positive drug) group, CLG low, medium, and high dose (2.36, 4.72, and 9.44 g·kg^-1) group. Mice were ig given corresponding drugs once a day for 14 consecutive days. On the 9th day of administration, 1 h after administration, except for the control group, 3 mg·kg^-1 scopolamine was ip for modeling. Y maze test was performed 20 min after the last dose. On the 15th day, the platform experiment was carried out, the brain was dissected, the brain weight was weighed, the brain body coefficient was calculated. The pathological changes were observed after HE staining. The contents of acetylcholine (Ach), acetylcholinesterase (AchE), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) in the hippocampus were determined by ELISA method. Results (1) Compared with control group, CLG dose groups had no significant effect on body weight, and the sleep rate of the diazepam group and the CLG high-dose groups tended to increase, but there was no significant difference. The sleep latency of the diazepam group and the CLG high-dose groups was significantly shortened (P<0.05), and the sleep time of the CLG high-dose groups was significantly prolonged (P<0.01). (2) Compared with model group, the number of platform jumps in donepezil group and CLG administration groups were significantly reduced (P<0.05), Ach of all CLG administration groups had an increasing trend, AchE of donepezil group, CLG middle and high dose groups had a decreasing trend, but there was no significant difference, and SOD was significantly increased and MDA was significantly decreased in CLG dose groups (P<0.05). Compared with model group, the pathological changes of cortex and hippocampus in CLG medium- and high-dose groups were significantly reduced. Conclusion CLG has sedative and hypnotic effects, and its effect on MCI improvement may be related to the regulation of cholinergic system and anti-oxidative stress.