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【答案】应助回帖
申请书摘要 以青龙衣活性部位(AE)为研究对象，以HPLC-DAD-MS为技术平台，采用代谢组学（metabonomics）的研究方法，通过对生物样品（如尿液、血清和组织）代谢物的分析，对应于体内抗肿瘤动物模型的药理学检测指标，从代谢物中筛选与抗癌活性有相关性的代谢物靶标（metabolite target）和代谢轮廓(metabolic profilng)。以代谢物靶标分析 和代谢轮廓分析为指导，开展中药青龙衣抗癌活性物质的追踪、筛选，研究青龙衣中具有抗癌活性的有效成分（群）及作用机理,解决目前中药青龙衣及其制剂中抗癌作用的物质基础不明确，作用机理不清楚的问题,为进一步开发以青龙衣为原料的抗癌新药奠定理论基础。 本项目利用代谢组学的研究思路和研究方法，建立了从中药复杂的"黑色"或"灰色"多组分体系中筛选抗癌活性物质新模式。
申请书主题词 青龙衣活性部位(AE)；HPLC-DAD-MS；代谢组学；抗癌活性
结题中文摘要 随着肿瘤对人体健康的危害日益严重，抗肿瘤研究已成为生命科学、化学等领域研究的热点。开发疗效高、选择性强、毒副作用低的新抗肿瘤药物，已成为抗肿瘤研究迫切需要解决的难题。本项目以青龙衣活性部位为研究对象，以HPLC-DAD-MS为技术平台, 代谢组学为研究方法，建立了筛选中药抗肿瘤活性成分的新模式。通过对青龙衣天然药物化学研究和生物样品（如尿液、血清和组织）代谢物的分析，开展中药青龙衣中抗肿瘤活性物质的追踪和筛选，研究青龙衣中具有抗肿瘤活性的有效成分（群）及作用机理；建立了青龙衣中目标化合物的分析方法并进行了有效成分药代动力学研究；结合代谢组学在中药毒性研究中具有的优势，以探讨中药青龙衣对健康小鼠代谢影响为目标，对给药小鼠血浆进行代谢图谱的分析，同时考察了青龙衣提取物对小鼠肝脏和肾脏形态学的影响。解决了目前中药青龙衣及其制剂中抗癌作用的物质基础不明确，作用机理不清楚的问题，为进一步开发以青龙衣为原料的抗肿瘤新药奠定理论基础。
结题英文摘要 Human health is being seriously threatened by cancer and the studies on the anticancer have become the focus in life sciences and chemistry areas. There is an urgent need to develop a kind of high efficacy, high selectivity and low toxicity anticancer drugs. In this project, a new model of the screening anticancer compounds from the husks of walnut (Juglans regia L.) (QLY) was set up based on the metabonomics and HPLC-DAD-MS methods. By the studies of natural products and the metabolic analysis of the biological samples, such as urine, plasma and tissues, the anticancer compounds were tracked and screened. And then, the analysis method of the target compounds in QLY was set up and the pharmacokinetics of active ingredients was also development. Due to the superiority of metabonomics in toxicology research of traditional Chinese medicine, the toxicology of QLY extracts were studied using HPLC based metabonomics. The disturbances of mice plasma induce by QLY extracts were profiled by metabolic fingerprint analysis and the histopathology of liver exposed to QLY extracts showed significant damage. In addition, the structures of these anticancer compounds and the mechanism of anticancer in traditional Chinese medicine QLY and preparations were elucidated. The results indicate that the unclear problems of material basis and mechanism were solved, which is the theoretical basis in the further development of anticancer drugs from the QLY. |
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