以防治大鼠失眠焦虑心肾不交证量效优选交泰丸制备工艺  

Optimization of the Preparation Process of Jiaotai Pills Based on the Dose-effect Relationship for Prevention and Treatment of Disharmony between Heart and Kidney Syndrome with Insomnia and Anxiety

作　　者：王宏雅 武晓玉 刘惠萍 丛旖君 赵欣[2] 蔡大勇[2] 张玉杰[1] Wang Hongya;Wu Xiaoyu;Liu Huiping;Cong Yijun;Zhao Xin;Cai Dayong;Zhang Yujie(School of Chinese Materia Medica,Bejing University of Chinese Medicine,Beijing 102488,China;Institute for Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]中国医学科学院药用植物研究所

出　　处：《中国药师》2021年第7期292-296,309,共6页China Pharmacist

摘　　要：目的:根据不同提取方法制备的交泰丸治疗大鼠失眠焦虑心肾不交证的量效关系,筛选最佳工艺。方法:采用每天随机束缚3 h且每周分别随机3次禁食禁水(24 h/次),连续21 d,建立大鼠失眠焦虑心肾不交证模型。d_(22)动物分组,灌胃给予梯度剂量8种不同工艺交泰丸(1.86186.7 mg·kg^(-1)·d^(-1),k=1.77),连续10周;d77采用戊巴比妥钠睡眠协同实验检测睡眠时间,高架十字迷宫(EPM)和旷场实验(OFT)观察焦虑相关行为学变化;d_(102)处死动物,苏木精-伊红(HE)染色观察海马CA3区病理变化,形态计量神经元细胞个数;ELISA检测血清五羟色胺(5-HT)、去甲肾上腺素(NE)含量;Graphpad Prism 5软件非线型可变斜率回归不同制剂工艺交泰丸的半数有效剂量(ED_(50))。结果:不同工艺制备的交泰丸治疗后,可不同程度延长大鼠睡眠时间,缓解焦虑行为,升高血清5-HT,降低NE水平,减轻海马CA3区病理改变;其量效曲线呈“S”型。优选出交泰丸最佳提取工艺为:黄连、肉桂水提两次(4 h/次),药液合并后减压干燥。结论:本实验通过治疗失眠焦虑心肾不交证量效实验,优选了交泰丸制备工艺,为后续药物研发与临床应用提供了依据。Objective:To confirm the optimal preparation process of Jiaotai pills according to the dose-effect relationship of Jiaotai pills with different extracting methods for treating insomnia and anxiety with disharmony between heart and kidney syndrome in rats.Methods:The insomnia and anxiety model in rats was induced by random bondage(3 hours a day)and fasting with water prohibition(24 hours each time,3 times a week)for 21 days.At d_(22),the rats were intragastrically administrated with gradient dosages of Jiaotai pills(1.86-186.70 mg·kg^(-1)·d^(-1),k=1.77)with eight different preparation processes for ten weeks.At d77,sleep-coordination test with pentobarbital sodium was used to detect insomnia,and elevated cross maze(EPM)and open-field experiment(OFT)were used to evaluate anxiety.The animals were sacrificed at d_(102),the pathological features were observed with hematoxylin-eosin(HE)staining,and the number of neurocytes in CA3 region of hippocampus was analyzed by morphometry.The serum levels of 5-hydroxytryptamine(5-HT)and noradrenaline(NE)were detected by ELISA assays.The ED_(50) was calculated by non-linear regression with various slopes using Prism-5.0 software to determine the optimal preparation process of Jiaotai pills.Results:Jiaotai pills prolonged sleeping time,alleviated anxiety,increased 5-HT level,decreased NE level and relieved pathological changes of hippocampus.The dose-response curves showed“S”shape.The optimal preparation technology was as follows:coptis chinensis and cinnamomum were extracted twice with water(4 hours each time),and the extracts were mixed for concentration and decompression drying.Conclusion:The study determines the optimal preparation of Jiaotai pills with the dose-effect relationship for treating insomnia and anxiety with disharmony between heart and kidney syndrome in rats,which provides basis for drug development and clinical application of Jiaotai pills in future.

关 键 词：交泰丸 失眠焦虑 心肾不交证 制备工艺 

分 类 号：R283.6[医药卫生—中药学] R285.5[医药卫生—中医学]