中药酸枣仁对斑马鱼睡眠剥夺模型的行为学及神经递质受体的影响  

Effects of Semen Ziziphi Spinosae on behavior and neurotransmitter receptor in zebrafish sleep deprivation model

作　　者：夏婧 游秋云[1] 黄攀攀[1] 丁莉[1] 赵宾宾[1] 高川 蔡铭 王平[1] XIA Jing;YOU Qiu-yun;HUANG Pan-pan;DING Li;ZHAO Bin-bin;GAO Chuan;CAI Ming;WANG Ping(Hubei University of Chinese Medicine,Wuhan,Hubei 430065,China)

机构地区：[1]湖北中医药大学

出　　处：《时珍国医国药》2019年第9期2061-2064,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(81573865)

摘　　要：目的观察酸枣仁对斑马鱼睡眠剥夺模型的睡眠改善及镇静作用,以及对γ-氨基丁酸(GABA)A型受体α1亚单位(GABRA1)、γ2亚单位(GABRG2)和谷氨酸(Glu)N-甲基-D-天冬氨酸受体2A亚单位(GRIN2Aa)、代谢型受体6亚单位(GRM6A)mRNA表达的影响。方法采用光刺激诱导活体斑马鱼建立睡眠剥夺模型,分别水溶给予不同浓度炒酸枣仁颗粒和艾司唑仑片,应用行为分析仪定量斑马鱼的运动距离和失眠时间,采用RT-PCR检测GABRA1、GABRG2、GRIN2Aa和GRM6A mRNA的相对表达量。结果在观察的1 h内,模型组斑马鱼运动时间和距离均高于正常对照组,差异有统计学意义(P<0.05)。低、中、高剂量的酸枣仁对睡眠的改善作用分别为0.43、2.21和3.33倍,镇静作用分别为0.97、1.47和2.00倍。与模型组比较,酸枣仁组4种受体mRNA相对表达量降低,其中低、中剂量组GABRA1和GABRG2 mRNA相对表达量明显降低(P<0.01),中、高剂量组GRIN2Aa和GRM6A mRNA相对表达量明显降低(P<0.01)。结论低、中、高浓度酸枣仁对斑马鱼睡眠剥夺模型的睡眠有显著改善作用;酸枣仁改善其睡眠的机制可能为调节神经递质受体的表达。Objective To observe the effects of Semen Ziziphi Spinosae on sleep improvement and sedation in zebrafish sleep deprivation model,and on the expression of gamma-aminobutyric acid(GABA)type A receptor alpha 1 subunit(GABRA1),gamma 2 subunit(GABRG2),glutamate(Glu)N-methyl-D-aspartate receptor 2 A subunit(GRIN2Aa),metabolic receptor 6 subunit(GRM6A)gene.Methods Sleep deprivation models were established by light stimulation.Different concentrations of parched Semen Ziziphi Spinosae granules and estazolam tablets were given to zebrafish in water respectively.The movement distance and time of zebrafish were quantified by behavioral analyzer.RT-PCR was used to detect the relative expression of GABRA1,GABRG2,GRIN2Aa and GRM6A mRNA.Results Within 1 hour of observation,the time and distance of zebrafish movement in the model group were higher than those in the control group,and the difference was statistically significant(P<0.05).The effects of low,medium and high doses of Semen Ziziphi Spinosae on sleep improvement were 0.43,2.21 and 3.33 times,and the sedative effects were 0.97,1.47 and 2.00 times,respectively.Compared with the model group,the relative expression of four receptors in Semen Ziziphi Spinosae groups were significantly lower,and the relative expression of GABRA1 and GABRG2 decreased significantly in low and medium dose groups(P<0.01),while the relative expression of GRIN2Aa and GRM6A in medium and high dose groups was significantly lower(P<0.01).Conclusion Low,medium and high concentration of Semen Ziziphi Spinosae can significantly improve the sleep of zebrafish sleep deprivation model.The possible mechanism of Semen Ziziphi Spinosae improving sleep is to regulate the expression of neurotransmitter receptors.

关 键 词：斑马鱼 睡眠剥夺 酸枣仁 Γ-氨基丁酸 谷氨酸 

分 类 号：R285.5[医药卫生—中药学]