泻心汤抗内毒素有效组分与吸收动力学研究

【作者】 何毓敏；

【导师】 张艺；

【作者基本信息】 成都中医药大学 ， 药物化学， 2006， 硕士

【摘要】 泻心汤为记载于《金匮要略》的经典名方，由大黄、黄连和黄芩三味药组成，具有泻火解毒、清热燥湿等功效，近代临床广泛应用于感染性疾病的治疗。 现代医学认为，感染性疾病的发生发展与内毒素(endotoxin)介导的炎症过程有密切关系，并且内毒素与中医“热毒”、“疫毒”有密切联系，因而中医临床治则基本遵循“清下并用，扶正祛邪”的原则。然而，现有泻心汤研究较少从有效组分的角度，深入研究其清热解毒与抗内毒素作用相关的药效物质基础及作用机理。本文紧密结合中医药理论，选择泻心汤抗内毒素有效组分为切入点，开展如下实验研究： 1．泻心汤抗内毒素有效组分(EFX)的确定 对泻心汤各拆方组进行了多项抗内毒素活性的药效学研究。结果表明，各拆方组均有不同程度的抗内毒素作用，其中大黄-黄芩药对活性优于原方及其它各拆方组。进一步研究发现该药对不同溶剂提取部位中，以正丁醇部位活性较优。结合化学预试，该部位主要含大黄蒽醌和黄芩黄酮，因此确定二者为泻心汤抗内毒素的主要有效组分。 分别提取分离得到了大黄蒽醌和黄芩黄酮，进行了二者的配比研究。大黄蒽醌和黄芩黄酮以一定的比例组方，进行配伍配比筛选试验，进一步确定了泻心汤抗内毒素最佳有效组分(EFX)。 采用HPLC梯度洗脱法，对EFX进行了指纹图谱初步研究，确认了各主要色谱峰，并为该有效组分建立了定性定量的质量控制方法。 2．EFX的吸收动力学研究 为进一步阐明EFX配伍的增效机制，从药物动力学角度比较了配伍前后有效组分中黄芩苷的吸收动力学特征。建立了两种门静脉吸收动力学的药物动力学模型，测定了黄芩苷的血药浓度-时间曲线，对相关参数进行了拟合。结果表明，配伍能提高黄芩苷在门静脉的血浆药物浓度，显著增加其吸收的程度。这为大黄黄芩配伍的合理性提供了证据，并对黄芩与大黄配伍后，药理作用的显著增加进行了药物吸收机制探索。 综上所述，本文进行泻心汤抗内毒素有效组分及吸收动力学作用机理研究，为进一步阐明泻心汤抗内毒素药效物质基础及作用机理提供了科学依据。更多还原

【Abstract】 Decoction for purging heart-fire, whose Chinese name is Xiexin Decoction, is a famous prescription mentioned in Jinkui Yaolue (Medical Treasures of the Golden Chamber). The decoction is made up of Radix et Rhizoma Rhei, Rhizoma Coptidis, and Radix Scutellariae, with function of purging fire and detoxifying, heat-clearing and damp-drying. Now, it is employed to treat infectious diseases in clinic.The modern medicine has explained the relations between the infectious diseases’ causes, processes, and consequences, and the inflammation induced by endotoxin (ET). According to theories of Traditional Chinese Medicine (TCM), ET is the representative of heat-toxin and pestilential poison, so the followed principles of treatment should be consistent with these theories, which are clearing and descending heat-toxin, supporting healthy energy to eliminate evils. But, the existing researches on Xiexin Decoction seldom follow these theories well, nor explore its fundamental substance or functional mechanism of clearing away heat-toxin and toxic material from a point of view of effective fraction. This article has carried out an integrative research based on theories of TCM, which focused on the effective fraction with anti-endotoxin activity of Xiexin decoction (EFX). The contents are as follows:1. The acknowledgement of EFXDismemberment study had been carried out including measuring and comparing some pharmacological indexes of anti-endotoxin activities. As a result, both whole ingredients and different ingredient groups had certain effects of anti-endotoxin at the different degree, and the effect of the ingredient group composed of Radix et Rhizoma Rhei and Radix Scutellariae exhibited better than the whole ingredients. Further researches on activities of anti-endotoxin in its different solvent extracting fraction showed that n-BuOH fraction had obvious antagonistic effect. Pre-experiment showed that fraction contained anthraquinones in Radix et Rhizoma Rhei and flavonoids in Radix Scutellariae. So it could be confirmed that these are main effective fractions in Xiexin Decoction.Then, the extractions with anti-endotoxin activity were extracted, isolated, and purified, and the proportion of them had been screening by pharmacological experiments. The result showed that compatibility of anthraquinones in Radix et Rhizoma Rhei and flavonoids in Radix Scutellariae exhibited the strongest activity更多还原