项目来源

国家重点研发计划(NKRD)

项目主持人

杨凌

项目受资助机构

上海中医药大学

立项年度

2017

立项时间

未公开

项目编号

2017YFC1702000

研究期限

未知 / 未知

项目级别

国家级

受资助金额

1898.00万元

学科

中医药现代化研究

学科代码

未公开

基金类别

“中医药现代化研究”重点专项

关键词

器官芯片 ; 有毒中药 ; 毒性评价 ; 致毒机制 ; 安全用药 ; Organ chip ; Toxic traditional Chinese medicine ; Toxicity evaluation ; Toxic mechanism ; Safe medication

参与者

王平；潘秋莎；于洋

参与机构AI

遵义医科大学;大连理工大学;苏州大学;上海中医药大学;吉林大学;黑龙江省生物医药重点实验室省部共建国家重点实验室培育基地哈尔滨医科大学;扬州大学

项目标书摘要：本项目依据中医药“以人为本，辨证论治”的思想，结合西医注重机制研究、证据健全和逻辑递进等优势，开展了肝脏芯片、心脏芯片等不同器官芯片的构建，及26种毒性中药的采集制备与毒效机制探索研究。目前，已构建了系列肝芯片，包括肝生理芯片，酒精肝芯片，免疫肝芯片；以及高仿生心脏芯片与肾芯片。制备标准提取物36个、组份56个，获得112个单体化合物。利用体外筛选技术，以心、肝、肠、肾等不同脏器损伤标志物以及微流控单器官芯片对26种有毒中药的提取物及其主要成分进行了筛选与评价。构建了中药心脏毒性评价标准，完成构建细胞、类组织/组织、动物模型，揭示部分心脏毒中药的量—时—毒—效关系。完成山豆根、商陆、吴茱萸3味中药的血浆中指标成分含量测定、外细胞毒性筛选、急性毒性试验、最大耐受量MTD、以及测定不同剂量、不同给药时间大鼠肝毒性指标的变化，获得“量—时—毒”关系。开展部分生物碱，黄酮，马卡因等主要药效及毒效成分的药药相互作用研究，发现了新的潜在制毒机制。发表学术论文101篇，申请国家发明专利9项，获得奖励13项。本项目以芯片为技术核心，结合组学等分析技术，以代谢异常及亚细胞特征性标志物的异常等手段评价毒性效应，为“有毒”中药的客观评价和安全使用提供科学依据。

Application Abstract: This project based on the idea of"people-oriented,syndrome differentiation and treatment"of traditional Chinese medicine,combined with the advantages of Western medicine focusing on mechanism research,sound evidence and progressive logic,the project carried out the construction of liver chip,heart chip and other different organ chips,and the collection and preparation of 26 kinds of toxic traditional Chinese medicine and the exploration of toxic mechanism.At present,a series of liver chips have been constructed including liver physiological chip,alcohol liver chip,immune liver chip,high bionic heart chip and kidney chip.36 standard extracts and 56 components were prepared,and 112 monomer compounds were obtained.Using in vitro screening technology,26 kinds of toxic traditional Chinese medicine extracts and their main components were screened and evaluated by using different organ damage markers such as heart,liver,intestine,kidney and microfluidic single organ chip.The cardiotoxicity evaluation criteria of traditional Chinese medicine were constructed,and the dose-time-toxicity effect relationships of some cardiotoxic herbs were revealed using cell,tissue and animal models.The contents of index components in plasma,the screening of extracellular cytotoxicity,the acute toxicity test,the maximum tolerance dose MTD,and the changes of hepatotoxicity indexes in rats with different doses and different administration time were completed,and the"dose time toxicity"relationship was obtained.Some alkaloids,flavonoids,Macain and other major pharmacodynamic and toxic components of drug interaction research,found a new potential mechanism of toxin production.Under the support of this project,101 academic papers have been published,9 national invention patents have been applied,and 13 awards have been obtained.This project takes chip as the core technology,combined with the analysis technology of omics,evaluated the toxic effect by means of metabolic abnormalities and subcellular characteristic markers,so as to provide scientific basis for objective evaluation and safe use of"toxic"traditional Chinese medicine.

项目受资助省

上海市

项目实施周期(年)

5