罗布麻叶水提物镇静催眠作用研究

Sedative and hypnotic effects of water extract of Apocynum venetum leaves

目的探讨罗布麻叶水提物(water extract of Apocynum venetum leaves,AVLWE)镇静催眠作用及机制。方法随机将ICR小鼠分为对照组、右佐匹克隆(阳性药,0.40 mg·kg^(−1))组和AVLWE低、中、高剂量(0.58、1.17、2.34 g·kg^(−1))组,每天ig给药1次,连续4周,每周称体质量;于末次给药前1 d给药60 min后,应用旷场视频分析系统检测各组小鼠5 min自主活动;于末次给药45 min后,各组动物ip 1%戊巴比妥钠(35 mg·kg^(−1),阈下催眠剂量),记录30 min内入睡潜伏期、入睡动物数、睡眠时间;结束后麻醉处死动物,取脑称质量并计算脑系数。SD大鼠分为对照组、模型组、右佐匹克隆(阳性药,0.27 mg·kg^(−1))组和AVLWE低、中、高剂量(0.40、0.81、1.62 g·kg^(−1))组,每天ig给药1次,连续4周,每周称体质量;除对照组外,给药第28、29天ip对氯苯丙氨酸(PCPA)制备大鼠失眠模型,给药结束称取脑质量并计算脑系数,取下丘脑,ELISA试剂盒法测定5-羟色胺(5-HT)、多巴胺(DA)和5-羟吲哚乙酸(5-HIAA)的含量。结果小鼠实验结果表明,与对照组比较,各给药组第1~4周体质量均显著降低(P<0.01);右佐匹克隆片和AVLWE中、高剂量组睡眠发生率均显著增加(P<0.05、0.01);右佐匹克隆片和AVLWE中、高剂量组睡眠时间显著延长(P<0.05);AVLWE低、中、高剂量组脑系数均显著升高(P<0.01)。大鼠实验结果表明,与对照组比较,AVLWE高剂量组第1~4周体质量均显著降低(P<0.05、0.01);与模型组比较,AVLWE高剂量组脑系数显著升高(P<0.05);右佐匹克隆片组、AVLWE高剂量组DA水平显著降低(P<0.05)、5-HIAA水平显著升高(P<0.01),AVLWE低、中、高剂量组5-HT水平显著升高(P<0.05、0.01)。结论AVLWE具有改善睡眠的作用,机制可能与上调下丘脑5-HT水平、下调DA水平有关。

Objective To explore the sedative and hypnotic effects of water extract of Apocynum venetum leaves(AVLWE)and its preliminary mechanism.Methods ICR mice were randomly divided into control group,dexzopicron(positive drug,0.40 mg·kg^(−1))group and AVLWE low-dose,medium-dose and high-dose groups(0.58,1.17,2.34 g·kg^(−1)),ig once a day for four weeks,and body weight was weighed weekly.After 60 min of administration one day before the last administration,open field video analysis system was used to detect 5 min autonomous activities of mice in each group.45 min after the last administration,animals in each group were given a subthreshold hypnotic dose of 1%pentobarbital sodium(35 mg·kg^(−1)),and the sleep latency,number of sleeping animals and sleep time within 30 min were recorded.After anesthesia,the animals were killed,the brain was weighed and the brain coefficient was calculated.SD rats were divided into control group,model group,dexzopicron(positive drug,0.27 mg·kg^(−1))group and AVLWE low-dose,medium-dose and high-dose groups(0.40,0.81,1.62 g·kg^(−1)),ig once a day for four weeks,and body weight was weighed weekly.Except for the control group,the insomnia model of rats was prepared by ip p-chlorophenylalanine(PCPA)on the 28th and 29th day of administration.At the end of administration,the brain weight was measured and the brain coefficient was calculated.The hypothalamus was taken and the contents of 5-hydroxytryptamine(5-HT),dopamine(DA)and 5-hydroxyindoleacetic acid(5-HIAA)were determined by ELISA kit method.Results The results of mouse experiment showed that compared with the control group,the body weight of each administration group was significantly decreased from week one to four(P<0.01).The incidence of sleep in dexzopiclone tablets and AVLWE medium and high dose groups was significantly increased(P<0.05,0.01);Sleep time of dexzopiclone tablets and AVLWE medium and high dose groups was significantly prolonged(P<0.05);The brain coefficients of AVLWE low-dose,medium-dose and high-dose groups were significantly increased(P<0.01).Experimental results in rats showed that,compared with control group,body weight of AVLWE high-dose group was significantly decreased from week one to four(P<0.05,0.01).Compared with model group,brain coefficient of AVLWE high-dose group was significantly increased(P<0.05);DA was significantly decreased(P<0.05)and 5-HIAA was significantly increased(P<0.01)in dexzopiclone tablet group and high dose AVLWE group,while 5-HT was significantly increased(P<0.05,0.01)in low,medium and high dose AVLWE groups.Conclusion AVLWE has the effect of improving sleep.The mechanism of action may be related to the content of 5-HT and DA.