【作者】 陈尧；

【导师】 周宏灏；

【作者基本信息】 中南大学 ， 临床药理学， 2009， 博士

【摘要】 中药是中华民族的国粹,也是目前中国医药卫生领域中不可分割的重要组成部分,是国家的优势和特色;中药拥有几千年的民族传统文化背景,使得中药流传至今,长盛不衰。众所周知,相对西药来说,中药成分复杂的多,因而人们很难从有效的中药中确定其中起作用的成分。中药单体成分的药理作用及机制研究是目前中药研究领域的一个分支。中药提取物的单体成分结构及作用类似于西药,经过提取、精制、纯化,已经大不同于原材料。传统中药的多成分结构使其所含某一单体成分的毒副作用受到其它成分抑制而大大削弱或消失,因此单体成分的毒副作用往往会凸显出来。中药与化学药物合用,可能通过影响药物代谢酶的活性机制,增加或降低合用药物的疗效或毒副作用,从而影响人体健康,但是目前关于中药及单体成分对人体药物代谢酶活性的影响报道不多。本学位课题主要研究了几种国内外常用中药及单体成分对药物代谢酶活性的影响,主要内容如下:1.CYP1A2、CYP2A6、NAT2和XO酶活性评价方法的建立和应用。2.槲皮素同时影响了体内CYP1A2、CYP2A6、NAT2和XO的活性及咖啡因的代谢。3.丹参酮ⅡA磺酸钠影响了CYP1A2的活性及咖啡因的代谢。4.六味地黄丸影响CYP1A2、CYP2A6、NAT2和XO的活性并影响咖啡因的代谢。5.姜黄素影响CYP1A2、CYP2A6、NAT2和XO的活性并影响咖啡因的代谢。6.金雀异黄酮影响CYP1A2、CYP2A6、NAT2和XO的活性并影响咖啡因的代谢。在临床用药中,中药可能通过影响药物代谢酶活性的途径,导致药物-药物相互作用的产生,其结果可表现为相加、协同或拮抗作用。因此,利用药物-药物相互作用的原理,适当采取多种药物联合治疗,往往比单一用药治疗效果更为理想,还可减轻药物的不良反应。所以探讨中药对药物代谢酶活性的影响,无疑有着重要的意义。更多还原

【Abstract】 Traditional medicines are the quintessence and an important part of Chinese culture, which owns a history for thousands of years, making its reputation spread all over the world.As we all know, compare to western medicines, the components of traditional medicines are complex, thus it is difficult to determine the effective ingredients from the raw materials. Study on the pharmacological effects and mechanisms of monomer compositions extracted from traditional medicines is a branch science of pharmacology. Similar to the western drugs, after extraction, refining, purification, traditional medicine has great difference to its raw material.Traditional medicines containe many components, the toxic side effects of one monomer composition might inhibited by others, thus the side effects of monomer composition might come out after purification.Traditional medicines probably influence the activity of drug metabolising enzymes, increasing or reducing the effectiveness of treatment or the toxicity of co-administrations and thereby affect human health, but research about traditional medicines on the activity of human drug metabolising enzymes is not much. Present studies mainly concen about the effect of commonly used traditional medicines on the activity of drug metabolising enzymes, the main contents are as follows:1. HPLC method for determination of the activities of CYP1A2, CYP2A6, NAT2 and XO in vivo and its application.2. The simultaneous effects of flavonoid quercetin on the activities of CYP1A2, CYP2A6, NAT2 and XO in healthy volunteers. 3. Effect of sodium tanshinoneⅡA sulfonate on the pharmacokinetics of caffeine, a substrate for CYP1A2 in vivo.4. The simultaneous effects of Liuweidihuangwan on the activities of CYP1A2, CYP2A6, NAT2 and XO in healthy volunteers.5. The simultaneous effects of genistein on the activities of CYP1A2, CYP2A6, NAT2 and XO in healthy volunteers.6. The simultaneous effects of curcumine on the activities of CYP1A2, CYP2A6, NAT2 and XO in healthy volunteers.In clinic, traditional medicines may affect the activities of drug metabolising enzymes, resulting to the emergence of drug-drug interactions, which may express as additive, synergistic or antagonistic effect. Following the principle of drug-drug interactions. Resonable use of the combined drugs will be more useful than one single medicine, and also may mitigate the adverse drug reaction. Therefore to explore the traditional medicines on the activities of drug metabolising enzymes undoubtedly becomes important significant.更多还原