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。

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 activity in the open field，the distance of activity in the central region and the number of times entering the central region were reduced in the rats in the Chinese medicine medium-dose group and the Diazepam group（P＜0.01）， the levels of serum OXA and OXB were significantly reduced（P＜0.01）， the expression of hypothalamic OX1R was significantly reduced（P＜0.01）， and the HE staining showed that a large number of neurons with perineurial interspace enlarged and the local glial cell hyperplasia. Conclusion Modified Banxia Shumi Decoction can improve insomnia and reduce anxiety in rats by down-regulating the levels of OXA and OXB in serum and the expression of OX1R in the hypothalamus.

R285.5

广东省中山市科技计划项目（编号：2019B1016）