基于“培土生金”研究多种RNA表达谱在衰老模型小鼠脾-肺微环境中的交互响应及党参的干预作用

The essence of the human body depends on the innate essence and acquired essence，and the acquired essence comes from the diet and breathing，which are mainly governed by the “spleen” and “lung”. According to the five elements, the “spleen” belongs to the earth, and the “lung” belongs to the metal. The theory of traditional Chinese medicine “strengthening earth to generate metal”, means the condition of lung relies on whether the physiological function of spleen is normal. Based on the theory of “strengthening earth to generate metal” and our previous researches, this project discusses the interaction responses of mRNA, miRNA and lncRNA exprssion profiles in spleen, lung, stomach, intestines and pancreas tissues of aging model mice, and also studies the interventional effects of Codonopsis pilosula, using high throughput microarray and bioinformatics. These studies may identify the specific mRNA, miRNA, and lncRNA in spleen, lung, stomach, intestines and pancreas tissues under the aging and anti-aging states, and build the regulatory networks of miRNA-mRNA and lncRNA-mRNA related with the digestion and respiration. This research can provide the scientific basis for revealing the molecular mechanisms of aging and anti-aging of Codonopsis pilosula, and finding the new molecular biomarkers of aging and anti-aging, and understanding the scientific connotation of “strengthening earth to generate metal”. Moreover, it can also provide a theoretical basis for the further development and utilization of Codonopsis pilosula, the Gansu genuine regional drug.

人体之精由先天之精和后天之精组成，后天之精源于饮食和呼吸，主要依赖于脾肺二脏；从五行关系看，脾属土，肺属金，培土生金，肺气充足与否，赖于脾之生化功能是否正常。本课题基于中医“培土生金”理论并结合前期党参抗衰老研究的相关工作基础，利用高通量检测手段与生物信息学方法，从转录组学水平探讨衰老模型小鼠“脾-肺微环境”实体脏器中多种RNA表达谱的交互响应及党参对其的干预作用。从而发现在衰老及党参抗衰老状态下小鼠脾、肺、胃等组织特异性表达的mRNA、miRNA和lncRNA，并进一步构建与脾胃运化和肺部呼吸相关的miRNA-mRNA以及lncRNA-mRNA调控网络。为揭示衰老及党参抗衰老的分子机理，建立新的衰老及抗衰老分子标记物，以及进一步认识“培土生金”的科学内涵提供依据，也为甘肃道地药材党参的深入开发利用提供理论基础。

本课题基于中医“培土生金”理论，利用高通量表达谱芯片，分析 mRNA、miRNA 和 lncRNA 表达谱在正常、衰老、党参干预三种状态下小鼠“脾-肺微环境”实体组织中的交互相应，找到与衰老和党参抗衰老相关的特异性表达 mRNA、miRNA 和 lncRNA，并在此基础上，通过生物信息学的方法构建多种 RNA 的调控关系网络，寻找可能有重要意义的节点，再利用实时定量PCR 技术对关键性的靶分子进行验证。本研究发现了党参干预胃肠道衰老相关基因（Fam132a、RORC、1200016E24Rik和LOC105243318）的表达调控和胰腺组织中关键基因（Eci1、Dpep1、Serpini2）的表达调控，解析了党参对衰老小鼠脾胃消化系统的干预和影响。另一方面，本研究也构建了肺组织在衰老及高剂量党参干预后的lncRNA-miRNA-mRNA（ceRNA）网络，发现mRNAs（Hif3a、Zbtb16和Plxna2）和lncRNA（NONMMUT063872）作为关键节点参与其中。本研究从传统中医理论出发，应用高通量组学技术和生物信息学分析，揭示了党参干预衰老模型小鼠消化与呼吸功能之间的分子联系，发现了新的衰老及抗衰老分子标记物，为深入了解“培土生金”的科学内涵提供了依据，也为甘肃道地药材党参的开发利用提供了理论基础。