肉苁蓉及其主要成分抗免疫衰老作用及其机制的研究与实效验证

With Kaplan-Meier survival analysis, we have confirmed the average life span of SAM-P8, one of widely accepted as an animal model of aging, was significantly extended by oral administration of extracts of Cistanche deserticola (ECDs). Simultaneously, the periphery na?ve T cell were recovered. Based on these primary data and traditional Chinese medical theory, the anti-immunosenescence effects of ECDs will be further investigated, including restoration of na?ve T cell production, T cell activation, NKTs, T cell homeostasis, and related cytokines which establish the connections between the different T cell sub-populations. After that, the mechanisms associated with these anti-immunosenescence and life apan prolongation effects will be investigated, which included inhibiting the age-related cell death of bone marrow derived mononuclear cell, delaying senescence of hematopoietic stem cell (HSC) and progenitors; decreasing intracellular ROS productions; blocking ROS induced DNA damages; regulating senescence related gene expressions, including p16，p53 and p21 gene expression. Additionally, whether or not the aged bone marrow microenvironment could be improved by ECDs will also be investigated. Based on the research results above, the real-time in-vivo roles of anti-immunosenescence by ECDs will be confirmed in SAMP8 aged mice undergone either bacteria infection, tumor cell transplantation, or influenza vaccination. The purpose is to provide the evidences for anti-aging theory and clinical application of this widely used Traditional Chinese drug for more than thousand years.

采用国际上常用的衰老模型，SAM-P8快速老化小鼠，经Kaplan-Meier 生存寿命实验，证明肉苁蓉提取物能够延长衰老期小鼠的平均寿命，并增加衰老机体外周初始T淋巴细胞（Na?ve T cell）的比例。本课题首先从免疫衰老（immunosenescence）入手，探讨肉苁蓉及其主要成分抗免疫衰老的作用。研究其对衰老小鼠的na?ve T细胞的生成、活化、内稳态（hemostasis）、NKT等异常变化的改善作用。并依据中医理论，即肉苁蓉具有"补肾、益髓、填精、延年"的作用，进一步对影响免疫衰老变化的上游关键因素，衰老骨髓细胞的保护作用、以及衰老相关基因（p16、p21和p53）表达的作用进行"追根溯源"的探究。随后对其抗免疫衰老的后果进行"实效验证"。以期阐明肉苁蓉及其主要成分抗衰老延长寿命的作用及其机制。不仅具有重要的学术价值，也具有良好的应用前景。笔者检索国内外尚无这些研究报道。

肉苁蓉是最常见的抗衰老中药，具有“补精血”、“益髓”、“延年”治疗“血枯”等功效。广泛地用于抗衰老以及各种老年病的防治。然而，肉苁蓉抗衰老，预防老年病的其作用原理仍未得以系统实验的证明。我们课题组采用SAM-P8快速老化小鼠，经Kaplan-Meier 生存寿命实验分析，证明了肉苁蓉能够延长已经步入衰老期的小鼠的平均寿命。肉苁蓉及其主要提取物通过干预内源性的ROS以及微环境所导致的骨髓干细胞损伤，抑制衰老相关基因（p16、p21和p53）的表达，保护衰老骨髓干细胞（Sca1+），恢复外周血及脾脏的初始T淋巴细（Naïve T cells: CD3+ CD44lowCD45RBhigh T cells (%)），恢复其活化状态（CD4+CD28+）及（CD8+CD28+），增加自然杀伤细胞（NK: CD3+CD49+）亚群的数量，同时保留调节性T细胞（Treg: CD4+CD25+CD127）的功能，从而延缓衰老免疫的发展。经验证，其增强免疫的作用可以转化为对衰老机体对预防接种反应（Influenza Vaccination）恢复。我们的研究首次系统阐明了肉苁蓉抗衰老免疫的作用机制。不仅具有重要的学术价值，也具有良好的应用前景。