离子液体对秀丽线虫的低剂量兴奋效应（Hormesis）及基于类胰岛素信号通路的作用机理研究

Ionic liquids have been widely used in the process of chemical reaction and separation because of their unique physicochemical properties, therefore their environmental exposure is inevitable, raising concerns about their potential environmental risk. Currently, studies have been focused on their direct toxic effects. Some work have shown that ionic liquids can induce hormesis, which is defined as stimulatory effects of low doses of substances known to be toxic at higher doses. However the mechanism of hormesis are only partly understood. This project aims to investigate the hormesis of imidazolium ionic liquids on Caenorhabditis elegans. The hermetic response of different biological endpoints will be studied after exposed to the imidazolium ionic liquids with different functional groups, and effect of ionic liquid structure on the response will be established. By utilizing C. elegans strains with mutant genes that involved in insulin-like signaling pathway, the roles of these genes in the induced hormesis will be investigated. To identify pathways activated by ionic liquids at hermetic and toxic levels, microarray analysis of C. elegans gene express will be performed. Results from this project can provide fundamental information to further our understanding of the hermetic dose response of ionic liquids, to extensively evaluate their environmental consequence, and to predict their ecological and health risk of long-term exposure at low doses.

离子液体由于其特有的理化性质被广泛应用于化学反应和分离过程，因此它的环境暴露不可避免，其潜在的环境风险受到国内外学者的关注。目前这方面的相关研究大部分都是考察其毒性作用，已有研究表明离子液体具有低剂量兴奋效应，但其作用机理尚不明确。本申请课题拟以离子液体为对象，系统考察离子液体对模式生物秀丽线虫作用的低剂量兴奋效应，筛选产生响应的生物学终点；利用线虫的一系列与类胰岛素信号通路相关的基因突变品系，解析该信号传导通路在离子液体诱导的hormesis效应中的作用；利用线虫表达谱芯片技术比较研究线虫对毒性和兴奋剂量离子液体产生响应的重要基因，探讨离子液体的作用机制。本课题的研究对于完善离子液体在低剂量范围的剂量效应关系，深入评价其环境暴露的生物学效应，以及预测低剂量长期暴露下潜在的生态和健康风险，有着重要的理论意义。

项目执行期间，以秀丽隐杆线虫为对象，考察不同取代基链长溴化咪唑类离子液体在不同浓度下对线虫具有hormesis效应的检测终点，发现离子液体对线虫寿命具有hormesis效应且有剂量-效应关系；解析了低浓度离子液体延长线虫寿命的作用机制，低浓度离子液体可能是通过ROS的去除和上调类胰岛素信号通路相关基因的表达来延长线虫的寿命；构建了咪唑类离子液体毒性预测的QSAR模型，该模型具有很好的稳定性与很强的预测能力；探索了咪唑类离子液体对线虫的慢性毒性，解析了秀丽线虫对咪唑类离子液体可能的解毒机制。该课题的研究可为完善离子液体的环境生态效应提供重要理论依据。该项目资助成果已在国际SCI刊物发表论文8篇，并多次参加国内外学术会议。