基于毒理基因组学与代谢组学技术的细辛肺毒性机理研究

Excessive use of drugs is the key problem related to clinical drug safety, effectiveness, rationality, which reflects the relationship among drug dose, effecty and toxicity. While the dose of Asarum prescribed by "Chinese Pharmacopoeia" does not quite match the actual clinical application,and it restricts the clinical safe, effective and reasonable application of Asarum.The preliminary research results of our.research group show that the toxity and side effect of Asarum is due to the.unprincipled overdose,and the toxity is mainly expressed as pulmonary toxicity. Therefore,our research group will study on the scientific connotation of different theraputic dose with different usage and the pulmonary toxity related to overdose.This study will adopt the overall research strategy bye using the technologies of data mining, metabonomics, and toxicogenomics.From this study ,We intend to provide a scientific basis for safe,effective and rational application of Asarum,and support to modifications of Asarum in the new "Chinese Pharmacopoeia" in the near future.

药物的过量使用是事关临床安全、有效用药的核心问题之一，而药典中细辛的规定剂量与临床实际用药不甚吻合，制约了临床安全、有效、合理地应用细辛。课题组前期研究结果表明，细辛的毒副作用多见于过量使用，而且以肺毒性最为常见。因此本课题组以细辛散剂过量使用产生毒性为突破口，采取整体性研究策略，利用数据挖掘、毒理基因组学、代谢组学技术深刻揭示细辛散剂过量使用产生肺毒性的科学内涵，为临床安全、有效、合理使用细辛提供科学依据，为新版《中国药典》有关细辛内容的修订和完善提供支持。

本课题组以细辛散剂过量使用产生毒性为突破口，采取整体性研究策略，利用数据挖掘、毒理基因组学、代谢组学技术初步揭示细辛散剂过量使用产生肺毒性的机制：肺细胞在细辛散剂的处理作用下，基于GPCR信号通路相关的Olfactory receptor途径被激活，说明细辛能诱导肺部细胞错误地识别小分子，细辛所导致肺毒性的分子机理为诱导细胞识别吸收过多小分子，产生了类似嗅觉细胞的功能；研究结果对于细辛用药剂量的选择，毒理药理的分子机制具有指导意义，为临床安全、有效、合理使用细辛提供科学依据。