基于唾液代谢组学变化探讨肾与唾相关的内在机制

The saliva is an important component part of the human body fluid, which includes the drool and the spittle and is dominated by the spleen and the kidney. Recently, the researchers have explored the intrinsic relations between the spleen and the saliva from the multi-indicator, multi-level and multi-angle, but the studies about the intrinsic mechanism between the kidney and the saliva as well as the different influences from the spleen and the kidney to the saliva are less. Obviously, this understanding about saliva is not comprehensive. The secretion and excretion of the saliva are not only dominated by the spleen but also closely related to the kidney. For the further exploration of the relation between the kidney and the saliva as well as the explanation of the scientific connotation about the conception that the kidney is associated with the saliva in its secretion, the subject is going to start with the animal experiments and the clinical researches; adopt the systematic biology methods such as the metabonomics and the bioinformatics; compare the saliva metabolic diversifications between animals and human in the spleen-deficiency syndrome, kidney-deficiency syndrome as well as the dynamic evolutive process from the normal constitution and the kidney-deficiency constitution to the kidney-deficiency syndrome; contrast the different influences from the spleen and the kidney to the saliva horizontally and the saliva metabolic dynamic diversifications from the kidney in different physiological and pathological processes vertically; probe the possible biomarkers and the preventive targets in the diseases onset and development process; investigate the relational intrinsic mechanism of the kidney and the saliva in multi-level and multi-angel both vertically and horizontally, not only providing the objective basis for the modernistic study about the theory on viscera and their manifestation of Chinese medicine, but also laying the foundations for the development of the clinical related disease noninvasive diagnostic techniques and the researches about the initial prevention and treatment of the diseases.

唾液是人体津液的重要组成部分，包括涎与唾，由脾肾所主。近年人们从多指标、多层次、多角度探究脾与唾的内在联系，而对肾与唾相关的内在机制及脾肾对唾液影响的差异研究较少，显然这对唾液的认识是不全面的。唾液的分泌与排泄不仅受脾的调控，与肾也有密切关系。为了进一步深入探讨肾与唾相关的内在机制，阐释"肾在液为唾"理论的科学内涵，本项目拟从动物实验和临床研究两个角度入手，应用代谢组学、生物信息学等系统生物学方法，研究比较动物和人体脾虚证候、肾虚证候及正常体质-肾虚体质-肾虚证候动态演变过程中唾液代谢组的变化，横向比较脾肾两脏对唾液的影响差异，纵向比较肾脏在不同的生理病理状态下唾液代谢组的动态变化，探索疾病发生发展过程中可能的生物标志物及其预防靶标，从纵横两个方面，多层次、多视角探讨肾与唾相关的内在机制。既为中医肾藏象理论的现代化研究提供客观依据，也为临床开展相关疾病无创伤诊断技术和早期防治研究奠定基础。

现代研究发现，唾液成分的改变与多种疾病的发生密切相关。由于唾液采集具有安全方便、无创伤、无血源性疾病传播的危险，患者无痛苦，易于接受等优点，因而对于唾液的研究受到人们越来越多的关注。近年来人们从多指标、多层次、多角度探究脾与唾的内在联系，而对肾与唾相关的内在机制及脾肾对唾液影响的差异研究较少，显然这对唾液的认识是不全面的。唾液的分泌与排泄不仅受脾的调控，与肾也有密切关系。本课题从动物实验和临床研究两个角度入手，应用代谢组学、生物信息学等系统生物学方法，研究比较了动物和人体脾虚证候、肾虚证候及正常体质—肾虚体质—肾虚证候动态演变过程中唾液代谢组的变化，横向比较了脾肾两脏对唾液的影响差异，纵向比较了肾脏在不同的生理病理状态下唾液代谢组的动态变化。结果发现，肾虚体质与肾虚证候之间以及二者与正常对照组之间，唾液的PH值、生化指标及部分代谢物都发生了相应的变化，且有显著性差异（P＜0.05或P＜0.01），说明在不同的肾虚状态下，唾液中的成分确实会发生相应的变化，证明了肾与唾的相关性。同时研究还发现，伴随着脾虚和肾虚状态的出现，唾液的PH值及相应的生化指标、代谢物质也发生了变化，说明涎唾都分泌于口，确实由脾肾共同所主，也进一步说明了中医学“脾在液为涎”“肾在液为唾”理论的科学性。上述变化的物质可能就是肾藏象相关疾病发生发展过程中的生物标志物及脾肾所主涎唾的差异。这一研究，既有助于阐释“肾在液为唾”理论的科学内涵，为中医肾藏象理论的现代化研究提供客观依据，同时也有助于寻找肾藏象相关疾病早期诊断的生物标志物，探索其预防靶标，为临床开展肾藏象相关疾病无创伤诊断技术和早期防治研究奠定基础，因此具有重要的理论价值和临床意义。