脑宁糖浆的镇静催眠作用及其对睡眠剥夺小鼠神经递质的影响  

Sedative and hypnotic effects of Naoning Syrup and its effects on neurotransmitters in sleep-deprived mice

作　　者：李子恒 陶正恒 杨元喜 汪宏章 吴威 游秋云[1] 王平[1] LI Zi-heng;TAO Zheng-heng;YANG Yuan-xi;WANG Hong-zhang;WU Wei;YOU Qiu-yun;WANG Ping(Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Taizi Pharmaceutical Co.,Ltd.,Jingmen 448000,China)

机构地区：[1]湖北中医药大学,湖北武汉430065 [2]湖北太子药业有限公司,湖北荆门448000

出　　处：《中成药》2022年第10期3164-3169,共6页Chinese Traditional Patent Medicine

摘　　要：目的研究脑宁糖浆的镇静催眠作用及其对睡眠剥夺小鼠脑组织睡眠相关神经递质的影响。方法将144只小鼠随机分为正常组,舒乐安定组,脑宁糖浆低、高剂量组,连续灌胃给药14 d后,各组小鼠进行戊巴比妥钠阈下、阈上睡眠实验和自主活动实验等行为学测试。将75只小鼠随机分为正常组,模型组,舒乐安定组,脑宁糖浆低、高剂量组,连续灌胃给药14 d后,采用多平台水环境睡眠剥夺72 h进行造模,造模期间继续给药;采用LC-MS法检测皮层中GABA与5-HT含量,ELISA法检测下丘脑中orexin水平,免疫组化法检测皮层中GABA_(A)R表达,RT-qPCR法检测皮层中GABA_(A)R、5-HT_(1A)R和下丘脑中orexin mRNA表达。结果与正常组比较,舒乐安定组和脑宁糖浆各剂量组睡眠潜伏期、自主活动时间、活动路程、活动速度均缩短(P<0.01),睡眠时间、入睡率均增加(P<0.01)。与正常组比较,模型组小鼠皮层中GABA、5-HT含量和皮层中GABA_(A)R阳性表达、GABA_(A)R及5-HT_(1A)R mRNA表达均降低(P<0.01),下丘脑中orexin水平及mRNA表达均升高(P<0.01);与模型组比较,各用药组以上指标均有改善(P<0.05,P<0.01)。结论脑宁糖浆对睡眠剥夺小鼠具有镇静、催眠作用,其机制可能是通过上调神经递质GABA和5-HT含量,上调GABA_(A)R和5-HT_(1A)R表达,下调orexin表达实现的。AIM To study the sedative and hypnotic effects of Naoning Syrup and its effects on sleep-related neurotransmitters in brain tissue of sleep-deprived mice.METHODS One hundred and forty-four mice randomly divided into the normal group,estazolam group,low and high dose Naoning Syrup groups were subjected to behavioral assessment by pentobarbital sodium subthreshold,suprathreshold sleep test and independent activity test following the 14 days of continuous corresponding intragastric administration.Seventy-five mice were randomly divided into the normal group,the model group,sulindadine group,low and high dose Naoning Syrup groups for 14-day continuous intragastric administration,with the model established by sleep deprivation in multi-platform water environment for 72 hours during which the administration continued.These mice had their contents of GABA and 5-HT in cortex detected by LC-MS;their level of orexin in hypothalamus detected by ELISA;their GABA_(A)R expression in cortex detected by immunohistochemistry;and their mRNA expressions of GABA_(A)R,5-HT_(1A)R in cortex and orexin in hypothalamus detected by RT-qPCR.RESULTS Compared with the normal group,estazolam group and each Naoning Syrup group shared shorter sleep latency,autonomic activity time,activity path and quicker activity speed(P<0.01),and increased sleep time and sleeping rate(P<0.01).Compared with the normal group,the model group was observed with decreases in contents of GABA and 5-HT in the cortex,positive GABA_(A)R expressions,and mRNA expressions of GABA_(A)R and 5-HT_(1A)R in the cortex(P<0.01);and increases in orexin level and mRNA expression in the hypothalamus as well(P<0.01).Each group intervened with the medical agent performed much better than the model group in terms of the aforementioned indicators levels(P<0.05,P<0.01).CONCLUSION Naoning Syrup works well on the sleep-deprived mice as a sedative and hypnotic,which may be associated with the up-regulation of the contents of neurotransmitters GABA and 5-HT,the expressions of GABA_(A)R and

关 键 词：脑宁糖浆 睡眠剥夺 镇静催眠 γ-氨基丁酸(GABA) 5-羟色胺(5-HT) OREXIN 

分 类 号：R285.5[医药卫生—中药学]