[關(guān)鍵詞]
[摘要]
目的 觀察復(fù)方薰衣草顆粒(CLG)鎮(zhèn)靜催眠及對輕度認(rèn)知功能障礙(MCI)模型小鼠的治療作用。方法 (1)CLG鎮(zhèn)靜催眠和抗抑郁、抗疲勞作用研究:以曠場訓(xùn)練結(jié)果為主要條件、體質(zhì)量為次要條件,隨機(jī)將79只ICR小鼠分為對照組、地西泮(3 mg·kg-1,化藥陽性藥)組、復(fù)方棗仁膠囊(12.3 mg·kg-1,中藥陽性藥)組和CLG低、中、高劑量(2.36、4.72、9.44 g·kg-1)組。采用戊巴比妥鈉閾下劑量催眠、曠場和轉(zhuǎn)棒實(shí)驗(yàn),觀察CLG對小鼠的一般狀態(tài)、睡眠潛伏期、30 min內(nèi)入睡比例和總睡眠時(shí)間以及行為學(xué)的影響。(2)CLG改善MCI作用研究:將60只昆明小鼠以Y迷宮實(shí)驗(yàn)訓(xùn)練結(jié)果為主要條件、體質(zhì)量為次要條件隨機(jī)分為對照組、模型組、多奈哌齊(3 mg·kg-1,陽性藥)組和CLG低、中、高劑量(2.36、4.72、9.44 g·kg-1)組,每天1次,連續(xù)ig給藥14 d,給藥第9天起,給藥1 h后,除對照組外,ip 3 mg·kg-1東莨菪堿制備MCI模型。于末次給藥20 min后進(jìn)行Y迷宮實(shí)驗(yàn);第15天進(jìn)行跳臺實(shí)驗(yàn);解剖取腦,稱取腦質(zhì)量并計(jì)算腦系數(shù);HE染色后觀察腦組織病理改變;取海馬,ELISA法測定乙酰膽堿(Ach)、乙酰膽堿酯酶(AchE)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)水平。結(jié)果 (1)與對照組比較,CLG各劑量對體質(zhì)量無明顯影響;地西泮組和CLG各劑量組入睡率有增高趨勢,但無顯著性差異;地西泮組和CLG高劑量組入睡潛伏期明顯縮短(P<0.05) ;各給藥組睡眠時(shí)間均顯著延長(P<0.01)。(2)與模型組比較,多奈哌齊組和CLG各劑量組跳臺次數(shù)均顯著減少(P<0.05);CLG各劑量組Ach有升高趨勢,多奈哌齊組和CLG中、高劑量組AchE有降低趨勢;CLG各劑量組SOD顯著增加,MDA顯著降低(P<0.05);CLG中、高劑量組小鼠皮層和海馬病理改變明顯減輕。結(jié)論 CLG具有鎮(zhèn)靜催眠作用,其改善MCI的作用可能與調(diào)節(jié)膽堿能系統(tǒng)和抗氧化應(yīng)激有關(guān)。
[Key word]
[Abstract]
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.
[中圖分類號]
[基金項(xiàng)目]
國家重點(diǎn)研發(fā)計(jì)劃"中醫(yī)藥現(xiàn)代化研究"專項(xiàng)課題(2018YFC1708003,2018YFC1708006);天山創(chuàng)新團(tuán)隊(duì)計(jì)劃項(xiàng)目(2020D14011);天山雪松項(xiàng)目(2020XS19);烏魯木齊市"優(yōu)秀青年科技人才培養(yǎng)"工程