马蹄香抗焦虑复方药效及机制初探
摘要
焦虑症(anxiety disorder)是一种以焦虑情绪为主的神经症,主要表现为发作性或持续性的焦虑、紧张、惊恐不安等焦虑情绪,并伴有自主神经紊乱、肌肉紧张与运动不安等症状。近年研究表明,我国普通人群中焦虑症的发病率日渐上升,严重者甚至影响到日常的生活及工作。目前临床最常用的抗焦虑药物虽有较好的抗焦虑作用,但也存在着大量的不良反应。焦虑症在传统中医药理论中属于“郁证”的范畴,中医药治疗焦虑症有着悠久的历史,积累了丰富的临床经验。据此,本课题以传统中医药理论和古今医家的临床实践经验为依据,结合市场需要,以疏肝解郁,养血安神为治则,采用现代药理学方法,对临床有效方剂马蹄香抗焦虑复方进行抗焦虑作用研究。该方由蜘蛛香、合欢皮、炒酸枣仁、灯心草四味药组成,主要用于治疗肝气郁结、心神不宁型焦虑症。
论文分为文献研究与实验研究两部分,文献研究部分分析了中药在抗焦虑方面的研究进展；从化学成分与药理作用两方面对马蹄香抗焦虑复方的组成药物进行了综述；讨论了焦虑症与“郁证”的关系；对常用焦虑动物模型高架十字迷宫、明暗箱的研究进展进行了概括。
实验部分主要采用小鼠高架十字迷宫实验(Elevated plus-maze test, EPM)、明暗箱实验(Light-dark box test, LDB)、自主活动实验、抗惊厥实验,对马蹄香抗焦虑复方的抗焦虑作用及机制进行了初步评价。共完成了以下八项工作,包括马蹄香抗焦虑复方有效剂量范围的研究、马蹄香最佳乙醇提取浓度的研究、马蹄香渗漉工艺与回流工艺的药效比较、马蹄香抗焦虑复方最佳配比的研究、马蹄香抗焦虑复方药效的验证、马蹄香抗焦虑复方作用机制的初步探讨、马蹄香抗焦虑复方镇静及抗惊厥作用的研究。
研究结果表明,马蹄香抗焦虑复方的最佳配比为马蹄香：炒酸枣仁：合欢皮：灯芯草=12：9：9：1；马蹄香采取35%乙醇回流工艺时复方药效最佳；在此组成及工艺条件下复方剂量在1.2-4.8g/kg/d范围内有抗焦虑作用,并呈量效关系,同时无镇静及抗惊厥作用;且复方的抗焦虑作用可能通过γ-氨基丁酸受体发挥。
本课题对临床专治肝郁气滞、心神不宁型焦虑症的验方—马蹄香抗焦虑复方,进行了初步药效学及机制的研究,为将其开发成新药奠定了药理学基础,为同类中药抗焦虑药物的研究提供了示例,丰富了中医药对焦虑症的治疗。
Anxiety disorder is characterized by persistent feelings of apprehension, tension, or uneasiness, which is increasing recent years in China. Benzodiazepines, as an widely used anxiolytic, have serious adverse effects, such as sedation, tolerance, withdrawn effect and so on. As the traditional Chinese medicine (TCM) has a long history for the treatment of anxiety and it is well known for little side effect. Therefore, we studied the combined decoction of Valeriana jatamansi Jones which has signifficant anxiolytics in clinical.
1. Literature Review:
We had reviewed the general situation of anxiolytic Chinese herbs, light-dark box test, elevated plus-maze test and the study of anxiety disorder in traditional Chinese medicine theory.
2. Experimental Study:
The purpose of this study was to characterize the anxiolytic-like, anticonvulsant, hypnosedative properties of combined decoction composed of Rhizoma et Radix Valerianae Jatamansi, Semen Ziziphi Spinosae, Cortex Albiziae and Medulia Junci.
Male ICR mice were treated combined decoction (1.2 g/kg,2.4 g/kg,4.8 g/kg), saline, the positive controls diazepam (2 mg/kg) orally for 10 days. Combined decoction ai the ratio of 12:9:9:1 (2.4,4.8 g/kg, p.o.) showed significant anxiolytic-like effects in EPM and LDB. When the Valeriana jatamansi Jones was refluxed in aqueous ethanol (35%), mice expressed difference to other methods. The effects of the combined decoction on spontaneous activity were assessed by numbers of spontaneous activities, respectively. However, all groups of decoction didn't reduce numbers of spontaneous activity but diazepam, compared to control group. Moreover, combined decoction also didn't reduce the latent period of convulsion. In addition, the anxiolytic-like effects of combined decoction in the EPM and light-dark box test were blocked by GABA (A) antagonist flumazenil (3mg/kg, i.p.).
In conclusion, these results suggest that the combined decoction has anxiolytic effect and acts via the GABA (A) receptors, but didn't present sedative and anticonvulsant effects.
论文分为文献研究与实验研究两部分,文献研究部分分析了中药在抗焦虑方面的研究进展；从化学成分与药理作用两方面对马蹄香抗焦虑复方的组成药物进行了综述；讨论了焦虑症与“郁证”的关系；对常用焦虑动物模型高架十字迷宫、明暗箱的研究进展进行了概括。
实验部分主要采用小鼠高架十字迷宫实验(Elevated plus-maze test, EPM)、明暗箱实验(Light-dark box test, LDB)、自主活动实验、抗惊厥实验,对马蹄香抗焦虑复方的抗焦虑作用及机制进行了初步评价。共完成了以下八项工作,包括马蹄香抗焦虑复方有效剂量范围的研究、马蹄香最佳乙醇提取浓度的研究、马蹄香渗漉工艺与回流工艺的药效比较、马蹄香抗焦虑复方最佳配比的研究、马蹄香抗焦虑复方药效的验证、马蹄香抗焦虑复方作用机制的初步探讨、马蹄香抗焦虑复方镇静及抗惊厥作用的研究。
研究结果表明,马蹄香抗焦虑复方的最佳配比为马蹄香：炒酸枣仁：合欢皮：灯芯草=12：9：9：1；马蹄香采取35%乙醇回流工艺时复方药效最佳；在此组成及工艺条件下复方剂量在1.2-4.8g/kg/d范围内有抗焦虑作用,并呈量效关系,同时无镇静及抗惊厥作用;且复方的抗焦虑作用可能通过γ-氨基丁酸受体发挥。
本课题对临床专治肝郁气滞、心神不宁型焦虑症的验方—马蹄香抗焦虑复方,进行了初步药效学及机制的研究,为将其开发成新药奠定了药理学基础,为同类中药抗焦虑药物的研究提供了示例,丰富了中医药对焦虑症的治疗。
Anxiety disorder is characterized by persistent feelings of apprehension, tension, or uneasiness, which is increasing recent years in China. Benzodiazepines, as an widely used anxiolytic, have serious adverse effects, such as sedation, tolerance, withdrawn effect and so on. As the traditional Chinese medicine (TCM) has a long history for the treatment of anxiety and it is well known for little side effect. Therefore, we studied the combined decoction of Valeriana jatamansi Jones which has signifficant anxiolytics in clinical.
1. Literature Review:
We had reviewed the general situation of anxiolytic Chinese herbs, light-dark box test, elevated plus-maze test and the study of anxiety disorder in traditional Chinese medicine theory.
2. Experimental Study:
The purpose of this study was to characterize the anxiolytic-like, anticonvulsant, hypnosedative properties of combined decoction composed of Rhizoma et Radix Valerianae Jatamansi, Semen Ziziphi Spinosae, Cortex Albiziae and Medulia Junci.
Male ICR mice were treated combined decoction (1.2 g/kg,2.4 g/kg,4.8 g/kg), saline, the positive controls diazepam (2 mg/kg) orally for 10 days. Combined decoction ai the ratio of 12:9:9:1 (2.4,4.8 g/kg, p.o.) showed significant anxiolytic-like effects in EPM and LDB. When the Valeriana jatamansi Jones was refluxed in aqueous ethanol (35%), mice expressed difference to other methods. The effects of the combined decoction on spontaneous activity were assessed by numbers of spontaneous activities, respectively. However, all groups of decoction didn't reduce numbers of spontaneous activity but diazepam, compared to control group. Moreover, combined decoction also didn't reduce the latent period of convulsion. In addition, the anxiolytic-like effects of combined decoction in the EPM and light-dark box test were blocked by GABA (A) antagonist flumazenil (3mg/kg, i.p.).
In conclusion, these results suggest that the combined decoction has anxiolytic effect and acts via the GABA (A) receptors, but didn't present sedative and anticonvulsant effects.
引文
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