白术水提物对拟人不良生活方式致失眠大鼠的作用及机制  

Effects and mechanism of Atractylodes macrocephala Koidz.aqueous extract on insomnia rats induced by anthropomorphic bad life style

作　　者：周衡朴 颜美秋 苏洁[1] 俞静静 魏柯健 牛壮伟 谢佳茏 彭喜 陈素红[2] 吕圭源[1] ZHOU Hengpu;YAN Meiqiu;SU Jie;YU Jingjing;WEI Kejian;NIU Zhuangwei;XIE Jialong;PENG Xi;CHEN Suhong;LYU Guiyuan(School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals,Zhejiang University of Technology,Huzhou 313299,China)

机构地区：[1]浙江中医药大学药学院,杭州310053 [2]浙江工业大学长三角绿色制药协同创新中心,湖州313299

出　　处：《中华中医药杂志》2025年第2期835-840,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：浙江省重点研发计划项目(No.2020C04020);浙江省重点实验室项目(No.2012E10002);国家自然科学基金项目(No.82003977)。

摘　　要：目的:探讨白术水提物对拟人不良生活方式致失眠模型大鼠的作用,并探讨其可能机制。方法:采用黑咖啡灌胃和长时间光照制备大鼠失眠模型,造模16周,第10周开始白术低、高剂量组大鼠灌胃白术水提物0.25、0.5g/kg,每日1次,连续6周。用药结束后测定自主活动、糖水偏好率,进行戊巴比妥钠诱导睡眠实验;ELISA法检测脑匀浆中γ-氨基丁酸(GABA)、谷氨酸(Glu)含量和血清中总胆固醇、甘油三酯、尿酸、葡萄糖含量;HE和尼氏染色观察大脑海马区病理变化;RT-PCR法检测海马组织中γ-氨基丁酸A型受体α_(1)(GABRA_(1))、谷氨酸脱羧酶(GAD)、γ-氨基丁酸转运体1(GAT1)mRNA表达。免疫组化法观察海马区GABRA1、GAT1和GAD蛋白表达。结果:与模型对照组比较,白术高剂量组大鼠睡眠时间显著延长(P<0.05),糖水偏好率和脑匀浆GABA含量显著增加(P<0.01),自主活动次数及脑匀浆中Glu含量,血清中总胆固醇、甘油三酯、葡萄糖含量显著减少(P<0.05,P<0.01),海马区细胞排列紊乱减轻,尼氏小体数量增加;海马区GABRA1、GAD mRNA及蛋白表达升高,GAT1 mRNA及蛋白表达降低(P<0.05,P<0.01)。结论:白术水提物能改善拟人不良生活方式所致失眠,其机制可能与调节GABA信号通路有关。Objective:To investigate the effects of Atractylodes macrocephala Koidz.aqueous extract on insomnia model rats induced by anthropomorphic bad life style and to explore its potential mechanisms.Methods:An insomnia model was induced in rats by intragastric administration of black coffee and prolonged light exposure for 16 weeks.Starting from the 10th week,rats in the Atractylodes macrocephala Koidz.low-and high-dose groups were administered Atractylodes macrocephala Koidz.aqueous extract at 0.25 g/kg and 0.5 g/kg,respectively,once daily for 6 weeks.Post-treatment,voluntary activity,sucrose preference,and pentobarbital-induced sleep tests were conducted.Enzyme-linked immunosorbent assay(ELISA)was used to determine the levels of-aminobutyric acid(GABA)and glutamate(Glu)in brain homogenates,as well as total cholesterol,triglycerides,uric acid,and glucose levels in serum.HE and Nissl staining were employed to observe pathological changes in the hippocampal region of the brain.RT-PCR was used to measure the mRNA expression of GABA type A receptorα_(1)(GABRA_(1)),glutamate decarboxylase(GAD),and GABA transporter 1(GAT1)in the hippocampal tissues.Immunohistochemistry was performed to observe the expression of GABRA_(1),GAT1,and GAD protein in the hippocampal area.Results:Compared with the model control group,the Atractylodes macrocephala Koidz.aqueous extract high-dose group exhibited prolonged sleep duration significantly(P<0.05),significantly increased sucrose preference ratio and GABA levels in brain homogenates(P<0.01),and significantly decreased spontaneous activity counts,Glu levels in brain homogenates,as well as total cholesterol,triglycerides,and glucose levels in serum(P<0.05,P<0.01).The disordered arrangement of hippocampal cells was alleviated,and the number of Nissl bodies increased.GABRA and GAD mRNA and protein expression levels in the hippocampal region were increased,while GAT1 mRNA and protein expression levels were decreased(P<0.05,P<0.01).Conclusion:Atractylodes macrocephala Koidz.aqueous extract can

关 键 词：白术 失眠 睡眠 Γ-氨基丁酸 γ-氨基丁酸转运体1 谷氨酸脱羧酶 海马体 

分 类 号：R285.5[医药卫生—中药学]