人参皂苷Rg1调控Wnt信号通路延缓造血干细胞衰老的机制研究

Stem cells senescence have been recognized as the lastest theories for explaning organism aging and the key reasons for geriatric diseases development. It is the most important for delaying body aging and preventing or treating geriatric diseases to search the ways of regulating stem cells senescence.We have studied the renationship between“Qi and Xue”theory of traditional Chinese medicine and hematopoietic stem cell(HSCs) function for 30 years. Our results have indicated that HSCs senescence is closely related to many geriatric diseases and ginsenosides Rg1, a major anti-aging ingredient in Panax ginseng, plays a very important role in delaying HSCs aging,repairing HSCs damage induced by aging agent and protecting the immune system and the hematopoietic system effectively.So far, the reseach works for ginsenoside Rg1 to adjust HSCs senescence only has been reproted by our research group. But the mechanism for Rg1 adjust HSCs senescence is not clear.The lastest study have suggested that Wnt signal pathways pay a very important role for regluating HSCs aging.Our recent work have indicated that Rg1 can clearly inhibited the key targets point in Wnt/β-catenin signal pathways. On the basis of our previous works, we shall closely combine the lastest modern theories of stem cell senescence with the traditional Chinese medicine principle of anti-age and stem cell. By building the models of HSC senescence in vivo and in vitro, we shall investigate the relationship between the Wnt/β-catenin signaling pathways involved in aging regulation and ginsenosides Rg1 delayed HSCs aging. The results of our studies will be important theoretical contribution for explaning aging and anti-age's biological mechanism in the aspect of stem cells; important application for preventing and treating the disease caused by HSCs aging; important value for promoting the innovation of traditional Chinese medicine stem cell theory;important siginificance for bluiding up research team of stem cells senescence.

成体干细胞衰老是人体衰老和老年性疾病发生与发展的最新学说，因此寻找调控干细胞衰老途径至关重要。我们30年的研究证明：中医学“气血”理论与干细胞功能密切相关。课题组将现代干细胞理论和衰老学说与传统中医学对干细胞认识和衰老理论结合已证明，人参皂苷Rg1是“补气”要药人参重要的抗衰老成分，它可调控造血干细胞（HSC）衰老，拮抗致衰剂对HSC损伤，但其分子机制不清楚。最新研究证明，Wnt信号通路在调控HSC衰老中起着重要作用。我们预实验提示，Rg1对该通路关键靶点有明确抑制作用。本课题旨在构建HSC体内外衰老模型，探讨人参皂苷Rg1在与Wnt信号通路对话中调控HSC衰老的新机制。课题将在理论上阐释现代干细胞衰老新理论与“补气生血”途径延缓HSC衰老新机理；在应用上为中药有效成分调控干细胞衰老提供实验依据；在技术上为干细胞衰老研究提供新思路与新技术；在学科建设上促进多学科合作和青年人才。

成体干细胞衰老是人体衰老和老年性疾病发生与发展的最新学说，因此寻找调控干细胞衰老途径至关重要。我们多年研究证明：中医学“气血”理论与干细胞功能密切相关。课题组前期证明，人参皂苷Rg1是“补气”要药人参重要的抗衰老成分，它可调控造血干细胞（HSC）衰老，拮抗致衰剂对HSC损伤，但其分子机制不清楚。近年研究证明，Wnt信号通路在调控HSC衰老中起着重要作用。本课题通过构建HSC体内与体外衰老模型，探讨人参皂苷Rg1在与Wnt信号通路对话中调控HSC衰老的新机制。主要研究内容：1.按照传统中医药衰老理论与现代HSCs衰老生物学理论，构建衰老小鼠模型，研究衰老小鼠HSCs生物学与人参皂苷Rg1对其衰老的调控：2.按照氧化应激损伤的现代衰老理论,建立HSCs体外衰老模型，研究HSCs体外衰老生物学与人参皂苷Rg1对HSCs衰老的调控；3.按照Wnt/β-catenin信号通路与干细胞衰老密切相关的衰老新理论，研究人参皂苷Rg1调控该信号关键靶点与延缓HSCs衰老的关系。主要研究成果：1.人参皂苷Rg1在体内外均能拮抗氧化致衰剂D-半乳糖对HSCs的致衰老作用；2.人参皂苷Rg1调控HSCs衰老与降低其氧化应激损伤有关；3.人参皂苷Rg1通过干预Wnt/ β-catenin信号通路关键靶点，从而阻滞通路激活，抑制D-半乳糖对HSCs的致衰老作用。本课题在理论上阐释了现代干细胞衰老新理论与“补气生血”途径延缓HSC衰老新机理；在应用上为中药有效成分调控干细胞衰老提供实验依据；在技术上为干细胞衰老研究提供新思路与新技术；在学科建设上促进多学科合作和青年人才。