"生长壮老取决于肾"与干细胞及其微环境相关变化规律的研究

'Human development and degeneration due to kidney function' is widely known as an essential part of 'kidney stores essence' theory, which is one of the critical theoretical innovations in traditional Chinese medicine (TCM). The advantage and distinctness of TCM in treating senile diseases by regulating kidney function has been widely and definitely noticed in clinical practice, especially in treating primary osteoporosis and Alzheimer disease. Therefore, in this research we plan to choose 1000 healthy people for epidemiologic survey to invest the physical activity in different age, which also indicates the procedure of 'the change of kidney pneuma from abundant to decline'. Meanwhile, we take the pathology of primary osteoporosis and AZ to stand for the aging change widely known caused by 'deficiency of kidney essence'. Combing the research above, we compared the 112cases each for 7 different age groups and 30 cases each for primary osteoporosis and AZ to detect the developing tendency of whole gene expression of human. In this way, we can explore the biological foundation of dependability between 'kidney stores essence' theory and stem cells and microenvironment. In this research we dedicate to demonstrate the connotation of 'kidney stores essence' theory, reveal the mechanism of aging or 'deficiency of kidney essence', analyze the regularity of the efficiency of 'regulating kidney function' in treating senile disease. We have full confidence in both theoretical and practical value of the conclusion from this research, which will provide more convincing evidence for the clinic and will innovatively develop and fulfill the viscera theory of TCM.

"肾藏精"脏象理论的科学内涵研究是中医基础理论创新的关键科学问题之一，"生长壮老"取决于肾为"肾藏象"理论的重要组成部分；中医"从肾论治"相关疾病特别是老年性疾病如原发性骨质疏松症、老年性痴呆在临床上具有特色和优势。因此，本研究拟解决的关键科学问题是：从人体生命活动"肾中精气由盛而衰"的各阶段生理状态（健康人流行病学调查1000例）和"肾精亏虚"衰老（原发性骨质疏松症、老年性痴呆）的病理状态，通过检测人类全基因表达谱（7个不同阶段健康人112例与原发性骨质疏松症、老年性痴呆各30例）的变化规律，重点探索中医"生长壮老取决于肾"与干细胞及其微环境具有相关性的现代生物学基础。研究目的在于部分阐明中医"肾藏精"理论的基本科学内涵，并揭示"肾精亏虚"衰老机制，解析相关疾病从肾论治临床疗效产生的内在规律，为提高临床疗效提供依据，不断发展和丰富中医脏象理论，具有重要的理论研究意义和应用价值。

“生长壮老取决于肾”为“肾藏精”藏象理论的重要组成部分，“从肾论治”老年性疾病如原发性骨质疏松症、老年性痴呆在临床上具有特色和优势。本研究主要内容与结果：（1）通过对生长壮老不同年龄段健康人1044例的流行病学调查，从整体水平明确“生长壮老取决于肾”的表征信息，在发、骨、齿、唾、耳目、肌肉、皮肤、二阴二便、生殖、智力等方面具有明显由盛而衰的趋势, SF-36问卷显示在躯体功能（PF）、生理职能（RP）、躯体疼痛（BP）、社会功能（SF）等生命健康质量方面亦具有明显由盛而衰的变化，提示生理状态老年人具有“肾精亏虚”的表现；（2）基于人类全基因表达谱检测，生长壮老7个年龄阶段84例健康状态（13723个基因表达探针）基因表达有一定变化规律，即10-19岁明显上调、50-59岁明显下调，与生物学过程、细胞组成、分子功能以及G蛋白信号通路、淋巴细胞活化、烟碱乙酰胆碱受体信号通路、细胞骨架调节、钙信号通路、白细胞介素信号通路等有关，从而调节微环境导致干细胞衰老或凋亡；（3）健康状态老年人与肾精亏虚证原发性骨质疏松症、老年性痴呆(各16例)比较，同证异病具有相同差异基因表达S100P上调、CX3CR1下调；由于疾病不同，差异基因表达又各具特点；（4）“肾精亏虚证”相同、同一疾病、而性别（体质）不同的差异基因表达，OP患者中男女性别呈现相同基因表达为SNX3上调，而女性差异基因表达120个上调，男性62个上调，56个下调；AD患者男女性别相同基因表达为S100P上调，而女性差异基因表达上调基因181个，下调基因3个，男性上调基因24个，下调3个。研究部分揭示"生长壮老取决于肾"与"肾精亏虚证"的科学内涵，解析相关疾病从肾论治临床疗效产生的内在规律，具有重要的理论研究意义和应用价值。研究成果参与获得辽宁省科技进步一等奖1项、中华医学科技二等奖1项；发表论文6篇；研究团队获得2015年中国骨质疏松学会“创新团队奖”。