紫河车冻干粉改善睡眠作用及机制研究  

Research on effect and mechanism of Ziheche lyophilized powder to improve sleep

作　　者：车云 任季禹 韩聪 黄绍菊 张云[3] 臧传宝 张姗姗[3] 付开玲 刘可春[3] 夏青 CHE Yun;REN Jiyu;HAN Cong;HUANG Shaoju;ZHANG Yun;ZANG Chuanbao;ZHANG Shanshan;FU Kailing;LIU Kechun;XIA Qing(Department of Obstetrics and Gynecology,the Country Hospital of Chenggu,Hanzhong 723200,China;Yinfeng Low Temperature Medical Technology Co.,Ltd.,Jinan 250000,China;Biology Institute of Shandong Academy of Sciences,Jinan 250013,China;Maternal and Child Health and Family Planning Service Center of Shanxian,Heze 274300,China)

机构地区：[1]陕西城固县医院妇产科,陕西汉中723200 [2]银丰低温医学科技有限公司,山东济南250000 [3]山东省科学院生物研究所,山东济南250013 [4]单县妇幼保健计划生育服务中心,山东菏泽274300

出　　处：《药物评价研究》2024年第2期316-322,共7页Drug Evaluation Research

基　　金：山东省科技型中小企业技术创新能力提升工程项目(2022TSGC1036,2022TSGC2003);山东省中央引导地方科技发展资金项目(YDZX2022164)。

摘　　要：目的研究紫河车冻干粉改善睡眠的作用及机制。方法利用ip氯苯丙氨酸(PCPA)法制备大鼠失眠模型,设置对照组、模型组和紫河车冻干粉低、中、高剂量(0.09、0.18、0.36 g·kg^(-1))组,每天ig给药1次,连续给药7 d,对照组和模型组ig等量去离子水。通过检测体质量增长量、一般观察、翻正实验、旷场实验、强迫游泳实验、悬尾实验评价紫河车冻干粉改善睡眠的作用;利用Western blotting技术检测γ-氨基丁酸转氨酶(GABA-T)、谷氨酸脱羧酶-65(GAD65)、γ-氨基丁酸转运体1(GAT1)蛋白的表达水平。结果与模型组比较,紫河车冻干粉低、中、高剂量组大鼠体质量增加量显著升高(P<0.01);中、高剂量紫河车冻干粉具有显著缩短睡眠潜伏期(P<0.05)、显著延长睡眠时间(P<0.01)的作用;高剂量紫河车冻干粉使大鼠中央格停留时间显著延长(P<0.01)、中央格穿格次数显著增多(P<0.05)、站立次数和修饰次数显著增多(P<0.01),说明高剂量紫河车冻干粉能够减轻失眠大鼠焦虑情绪,增强自发探索活动能力;高剂量紫河车冻干粉使大鼠漂浮时间缩短(P<0.05),挣扎时间延长(P<0.01),说明高剂量紫河车冻干粉能够减轻失眠大鼠的抑郁状态。Western blotting结果显示,与模型组相比,紫河车冻干粉处理组大鼠下丘脑组织中GABA-T的表达水平显著降低(P<0.05),GAD65、GAT-1的表达水平显著升高(P<0.05、0.01)。结论紫河车冻干粉可能通过调控GABA-T、GAD65、GAT-1蛋白的表达水平,发挥改善睡眠的作用。Objective To study the sleep-improving effect and mechanism by of Ziheche lyophilized powder(ZLP).Methods To establish the rat insomnia model by intraperitoneal injection of chlorophenylalanine(PCPA).The rats were divided into control group,model group,and low,medium,and high concentration groups(0.09,0.18,and 0.36 g·kg^(-1)) of ZLP.Ig once a day for seven consecutive days,with the control group and model group receiving an equal amount of deionized water.The effect of ZLP on improving sleep was evaluated through general observation,righting experiment,open field experiment,forced swimming experiment,and tail suspension experiment,and the Western blotting technique was used to detect the expression levels of GABA-T,GAD65,and GAT-1 proteins,and preliminarily explore the mechanism of ZLP in improving sleep.Results Compared with the model group,the body weight increase of rats in the low,medium,and high dose groups of ZLP was significantly increased(P <0.01),medium and high doses of ZLP have the effect of shortening sleep latency(P < 0.05) and prolonging sleep time(P < 0.01),a high dose of ZLP prolonged the retention time of the central grid(P < 0.01),increased the number of times the central grid was pierced(P < 0.01),and increased the number of standing and modification times in rats(P < 0.01),indicating that high-dose ZLP can reduce anxiety in insomnia rats(P < 0.05) and enhance their spontaneous exploration activity ability(P < 0.01);high dose ZLP shortened the floating time(P < 0.05) and prolonged the struggling time of rats(P < 0.01),indicating that high-dose ZLP can alleviate the depressive state of insomnia rats.Western blotting results showed that compared with the model group,the expression level of GABA-T in the hypothalamic tissue of rats treated with ZLP decreased(P < 0.05),while the expression levels of GAD65and GAT-1 increased(P < 0.05 and 0.01).Conclusion ZLP may improve sleep by regulating the expression levels of GABA-T,GAD65,and GAT-1 proteins.

关 键 词：紫河车冻干粉 改善睡眠 蛋白免疫印迹 GABA能系统通路 作用机制 

分 类 号：R285.5[医药卫生—中药学]