中文摘要
中药香加皮强心、抗肿瘤等作用明显,但因其具有心脏毒性而限制了临床应用。本课题在前期研究的基础上,以香加皮、三七为研究对象,提出了“肠道微生态介导香加皮、三七配伍减毒作用”的科学假说,拟通过揭示肠道菌群、药代标示物、机体内源性成分及毒性之间的相互联系,达到阐明其配伍减毒作用机理的目的。课题拟先采用PCR-DGGE结合荧光定量PCR法,考察香加皮、三七配伍前后对大鼠肠道菌群产生的影响;再利用MDF技术结合LC-MS/MS法对配伍前后大鼠体内高暴露药物成分进行定性、定量分析,寻找与配伍减毒有关的药代标示物;并以H9C2为模型细胞,利用高内涵筛选技术,对药代标示物的潜在心脏毒性进行快速评价;最后利用代谢组学的方法考察配伍对大鼠内源性成分的影响,寻找与配伍减毒有关的生物标记物。本研究从肠道微生态、药物、机体相互作用的角度阐明香加皮、三七配伍减毒的物质基础和作用机理,为中药配伍减毒研究提供了新视角。
英文摘要
Cortex periplocae, which is the root bark of Periploca Sepium Bunge has been reported possess cardiac and anti-tumor effects, but the cardiotoxicity of cortex periplocae seriously affected the security of clinical application. Based on the former research, this study puts forward scientific hypothesis “cortex periplocae and panax notoginseng for toxicity reduction caused by compatibility through mediating of gut microbiota”. By revealing the relevance of gut microbiota, pharmacokinetic makers, biomarkersand toxicity, the mechanisms of compatibility will be clarified. In order to find out the effect of the gut microbiota by compatibility, PCR-DGGE and fluorescent quantificative PCR method will be used to measured the difference of the intestinal flora; after that, metabolomics study will be used to found the biomakers which influence by compatibility; and mass defect filtering (MDF) combined with LC-MS/MS method will be used to found the pharmacokinetics makers about attenuate toxicity; at last, evaluation method for high content screening system was employed to assess the cardiotoxicity of the pharmacokinetics makers. This study will clarify the compatibility material basis and mechanism of cortex periplocae and panax notoginseng by the interaction of gut microbiota, drug and organism. It can provide a new prospect for TCM compatibility mechanism research.
