三七多糖基于脂肪酸代谢途径延缓秀丽线虫衰老的分子机制研究

Ageing constitutes the most important risk factor for all major chronic ailments. Aging affect the quality of elderly people's life and also bring tremendous pressure and massive challenges to society. The polysaccharides exacted from plants are promising natural anti-aging supplements due to their low side effects. Our previous studies showed the polysaccharide from Panax notoginseng, a medicinal plant, could significantly extend the lifespan of Caenorhabditis elegans. Moreover, its lifespan prolongation effect may act via regulating the fatty acid metabolism. We wonder whether the fatty acid metabolism-related genes are regulated by P. notoginseng polysaccharide to delay aging, through the GC-MS, oil red O staining, qRT-PCR and so on. On this basis, we will construct the function-loss mutants using RNA interference in C. elegans. The detailed molecular mechanism will be investigated using green fluorescent protein quantification, western blot, lifespan assay and so on. This study will reveal a novel anti-aging signal pathway related by plant polysaccharides. And it will also provide a theoretical basis for the development of anti-aging drugs and broaden the application of P. notoginseng polysaccharides in the medical field.

衰老是人类主要疾病的重要风险因子，不仅严重影响老年人的生活质量，也给社会发展带来巨大压力和挑战。植物多糖因其低毒副作用，成为潜在的天然抗衰老的补充剂。本项目组前期以秀丽线虫为模型从药用植物三七主根中获得具有显著延寿功能的多糖组分MRP5，且发现其延寿功能可能与脂肪酸代谢有关。因此，本项目拟利用GC-MS、油红O染色、qRT-PCR等技术方法，考察三七多糖是否调节秀丽线虫脂肪酸代谢相关基因来影响寿命；在此基础上，进一步采用RNA干扰技术构建功能缺失线虫突变体，并结合绿色荧光蛋白定量、蛋白免疫印迹、寿命实验等阐释三七多糖通过调节脂肪酸代谢来延长线虫寿命的分子机制。本项目将阐释植物多糖抗衰老调控机制的又一新途径，也为抗衰老药物研发提供理论依据，拓宽三七多糖在医学领域的应用。

随着人类生活条件和医疗条件的提高，人们不仅期待拥有更长寿命，而且更追求在寿命延长的同时无疾病伴随状态，即延长健康寿命。植物多糖因其化学结构多样性和多靶点特性具有抗氧化、抗衰老、降血脂等功效。三七[Panax notoginseng（Burk）F. H. Chen] 属于五加科（Araliaceae）人参属（Panax）植物，是中国传统药食同源植物，其富含皂苷、多糖等活性成分。课题组前期从三七主根中获得具有显著延寿功能的多糖，但其延寿作用机制尚不清楚。本项目利用秀丽线虫，研究了三七多糖调节秀丽线虫脂肪酸合成代谢影响，发现三七多糖显著提高了秀丽线虫体内棕榈油酸（C16:1）和油酸（C18:1n9）在内的单不饱和脂肪酸含量，表明三七多糖延长线虫寿命的效果依赖单不饱和脂肪酸的合成。功能性转录因子研究显示，三七多糖可以显著诱导FOXO转录因子DAF-16以及脂肪代谢调控转录因子SBP-1和MDT-15表达，进而调控不饱和脂肪酸合成途径，并且外源施加油酸（C18:1n9）可以恢复三七多糖在功能缺陷突变体的延寿效果。本项目结果可以填补植物多糖对脂肪酸调节和延长健康寿命的关系，进一步丰富糖生物学理论，对开发多糖相关药物及功能食品的研究有着广泛的意义。