贝类异源物核受体介导贝体中腹泻性贝毒代谢解毒的机制研究

腹泻性贝毒（DSP toxins）是一类重要的贝毒素，具有细胞毒性、遗传毒性和神经毒性等，并具有促癌作用。但贝类对DSP毒素存在一定耐受性，这种耐受性与毒素在贝体内的代谢解毒过程有关。我们推测，异源物核受体可能通过介导贝体中重要代谢解毒酶和转运蛋白的表达，影响DSP毒素代谢过程，进而减轻毒素对贝的毒性。项目拟以翡翠贻贝为研究对象，采用转录组分析、权重基因共表达网络分析、qPCR、RNAi技术、石蜡切片技术等，分析和鉴定翡翠贻贝体内可能存在的异源物核受体，进一步通过对DSP毒素染毒后贝类不同组织中异源物核受体以及重要代谢解毒基因的表达变化及其关联性分析，重要核受体受到影响时贝类对DSP毒素的毒性响应变化研究等，阐释异源物核受体及重要代谢解毒基因的表达、毒素积累以及贝类对DSP毒素毒性响应的关系，解析贝类异源物核受体介导DSP毒素代谢解毒的机制，为深入认识贝类对DSP毒素的耐受机制奠定基础。

As one of the most important phycotoxins, diarrhetic shellfish poisoning toxins (DSP toxins) have a variety of toxicities including cytotoxicity, genotoxicity, neurotoxicity, as well as the tumor promoting activity in cell lines. However, it has been found that bivalves have some resistance to DSP toxins, which might be related to the metabolic detoxification of DSP toxins in bivalve species. In our previous studies, we found that CYP3A4, GST, P-gp and MRP were involved in the metabolic detoxification of DSP toxins in bivalves. However, the regulation of these key detoxification genes remains unclear. Nuclear xenobiotic receptors (NXRs), belonging nuclear receptor family, regulate genes involved in drug metabolism such as phase I cytochrome P450, phase II transferases and phase III drug transporters. Here, our objective is to learn if and how NXRs regulate metabolic detoxification of DSP toxins in bivalves. To this end, firstly, we shall identify possible NXRs in the mussel Perna viridis. Secondly, changes in expression of some important NXRs and key detoxification genes in bivalves after exposure to DSP toxins-producing dinoflagellate Prorocentrum lima will be observed, and the potential relationship between them will be analyzed. Finally, changes in response to DSP toxins in bivalves will be investigated when the important nuclear receptors are affected. Transcriptome analysis, weighted gene co-expression network analysis, RT-qPCR, RNAi technology and paraffin section technique, etc. will be employed in our study. Our study might provide more information about metabolic detoxification and resistance mechanism to DSP toxins in bivalves.