加味半夏秫米汤对失眠模型大鼠下丘脑食欲素及其受体的调控作用  

Regulatory Effect of Modified Banxia Shumi Decoction on Orexin and Its Receptor in Hypothalamus of Insomnia Model Rats

作　　者：赖康安 李青 胡莹 车思锦 李亮 LAI Kang-An;LI Qing;HU Ying;CHE Si-Jin;LI Liang(Dept.of Geriatrics,Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine,Zhongshan 528400 Guangdong,China;Dept.of Sleep Specialist,Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine,Zhongshan 528400 Guangdong,China)

机构地区：[1]广州中医药大学附属中山中医院老年病科,广东中山528400 [2]广州中医药大学附属中山中医院睡眠专科,广东中山528400

出　　处：《广州中医药大学学报》2024年第4期995-1002,共8页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广东省中山市科技计划项目(编号:2019B1016)。

摘　　要：【目的】观察加味半夏秫米汤对对氯苯丙氨酸(PCPA)诱导的失眠模型大鼠的治疗作用及机制。【方法】将48只雄性SD大鼠随机分成6组,即正常组,模型组,中药低、中、高剂量组和地西泮组,每组8只。造模前连续7 d,中药低、中、高剂量组大鼠分别给予加味半夏秫米汤进行预防性治疗。除正常组外,其余各组大鼠均构建PCPA诱导失眠模型。第1天造模后,各组继续对应给药,连续7 d。监测体质量,进行旷场试验行为学检测,采用酶联免疫吸附分析(ELISA)检测血清中食欲素A(OXA)和食欲素B(OXB)含量,免疫组织化学法检测下丘脑食欲素受体1(OX1R)的表达,苏木素-伊红(HE)染色法观察大鼠下丘脑的病理变化。【结果】(1)造模前各组大鼠体质量增长趋势平稳,组间无明显差异;造模后除正常组外,其余各组大鼠体质量增长速度减缓甚至下降;给予加味半夏秫米汤14 d后,与模型组比较,中药中剂量组大鼠体质量上升显著(P<0.01)。(2)与正常组比较,模型组大鼠在旷场中活动总距离、中央区域的活动距离及进入中央区域的次数增加(P<0.01),血清OXA和OXB含量显著升高(P<0.01),下丘脑OX1R的表达显著升高(P<0.01),HE染色显示下丘脑胶质细胞轻度增生;与模型组比较,中药中剂量组和地西泮组大鼠在旷场中活动总距离、中央区域的活动距离及进入中央区域的次数减少(P<0.01),血清OXA和OXB含量显著降低(P<0.01),下丘脑OX1R的表达显著降低(P<0.01),HE染色显示大量神经元周围间隙增大,局部胶质细胞轻度增生。【结论】加味半夏秫米汤可通过下调血清中OXA和OXB的含量及下丘脑中OX1R的表达来改善大鼠失眠,减轻大鼠焦虑状态。Objective To observe the therapeutic effect and mechanism of Modified Banxia Shumi Decoction on p-chlorophenylalanine(PCPA)-induced insomnia model rats.Methods Forty-eight male SD rats were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Chinese medicine and the Diazepam group,with 8 rats in each group.For 7 consecutive days before modeling,rats in the Chinese medicine low-,medium-and high-dose groups were treated with Modified Banxia Shumi Decoction for prophylactic treatment.Except for the normal group,PCPA-induced insomnia rat model was established in all groups.After modeling on day 1,each group continued to be administered the corresponding drug for 7 days.Body mass was monitored,open-field behavioral tests were performed,serum levels of orexin A(OXA)and orexin B(OXB)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of hypothalamic orexin receptor 1(OX1R)was determined by immunohistochemistry,and hematoxylin-eosin(HE)staining was used to observe the pathologic changes in the hypothalamus of rats.Results(1)Before modeling,the growth trend of body mass of rats in each group was smooth,with no significant difference between groups;after modeling,except for the normal group,the growth rate of body mass of rats in each group slowed down or even declined;after 14 days of administration of Modified Banxia Shumi Decoction,the body mass of the Chinese medicine medium-dose group was significantly increased compared with that of the model group(P<0.01).(2)Compared with the normal group,the model group showed an increase in the total distance of activity in the open field,the distance of activity in the central region and the number of times of entering the central region(P<0.01),a significant increase in serum OXA and OXB contents(P<0.01),a significant increase in the expression of hypothalamic OX1R(P<0.01),and HE staining showed mild hyperplasia of the hypothalamic glial cells;compared with the model group,the total distance of activ

关 键 词：加味半夏秫米汤 失眠 食欲素A(OXA) 食欲素B(OXB) 食欲素受体1(OX1R) 对氯苯丙氨酸(PCPA) 大鼠 

分 类 号：R285.5[医药卫生—中药学]