石斛碱抗衰老作用及机制研究

Aging, a process of degenerative changes of body's tissues and organs with the increase of age, is a risk factor for many diseases associated with age. Our previous study found that alkaloids of dendrobium nobile can improve glucose and fat metabolism disorder, which is very similar with function of metformin, and reduce the symptoms of AD in animal models. The further results suggest that alkaloids also induce autophagy flux in vitro. Dendrobine accounted for about 92.6% of the alkaloids, so it should be responsible to pharmacological action mentioned above. Subsequently, we found dendrobine can inhibit mTOR signaling pathway in PC12 cells in our pre-experiment. Growing evidences show the pathogenesis of aging and many age-dependent diseases involve mTOR signaling pathway dysfunction. In this study we will use two kinds of animal subjects Caenorhabditis elegans and sensecence accelerated mouse (SAMP8) to confirm effects of dendrobine anti-aging, and to screen the targets of dendrobine anti-aging effect focusing specifically on mTOR signaling pathway by transcriptional and proteomic techniques. To most important one or two targets, we will further verify the function mechanism of dendrobine anti-aging by employing the inhibitors or agonists, gene knockdown or overexpression. We will make clear the effects and mechanisms of dendrobine inhibiting aging, which will provide scientific basis for potential application of dendrobium nobile and dendrobine in the treatment of aging.

衰老是指机体各组织、器官功能随年龄增长而发生退行性变化的过程，是各种老年病发生的危险因素。我们前期研究发现金钗石斛生物碱具有类似二甲双胍调节糖、脂代谢的作用，并能改善AD模型动物学习记忆功能。进一步实验表明金钗石斛生物碱能够诱导自噬。我们的研究还表明石斛生物碱中石斛碱占92.6%，是发挥上述作用的主要成分，预实验发现石斛碱可抑制PC12细胞mTOR信号通路。大量研究证实mTOR信号通路调控与衰老和老年病的发生发展密切相关。本研究拟选用秀丽隐杆线虫和快速老化小鼠（SAMP8）两种动物模型观察石斛碱的抗衰老效应，并通过转录组学和蛋白组学技术，围绕mTOR信号通路深入研究石斛碱抗衰老的作用靶点，最后选择针对靶点的抑制剂或激动剂、基因敲除或过表达等措施探明石斛碱抗衰老的作用机制，以期为石斛和石斛碱抗衰老应用提供科学依据。

衰老是指机体各组织、器官功能随年龄增长而发生退行性变化的过程，是各种老年病发生的危险因素。我们前期研究发现金钗石斛生物碱具有类似于二甲双胍调节糖、脂代谢的作用，并能改善AD模型动物学习记忆功能。进一步实验表明金钗石斛生物碱能够诱导自噬。本研究拟选用秀丽隐杆线虫和快速衰老小鼠（SAMP8）两种动物模型观察金钗石斛生物碱的抗衰老效应。研究发现金钗石斛生物碱可以延缓秀丽隐杆线虫衰老，其机制与上调 daf-16、skn-1基因，提高抗氧化应激能力有关。同时，金钗石斛生物碱还可以延缓12月龄SAMP8小鼠的衰老，其作用机制可能与上调Klotho蛋白，减少Aβ聚集、增强自噬活性有关。金钗石斛生物碱还可以改善10月龄SAMP8小鼠的认知障碍，其机制与抑制内质网应激信号通路, 逆转异常磷酸化蛋白有关。