“肾应冬”生理机制的研究——时令季节对肾上腺轴功能影响的相关性研究

Kidney Corresponds with Winter is an indispensable part of Five Zang Organs Proper to the Season Theory in Inner Canon of Huangdi. It emphasizes that the physiological functions of kidney accommodate seasonal changes and a specificity of synchronous changes in the winter exists, which reflects the distinct thinking pattern in Chinese medicine of exploring features and functions of zang and fu organs. This study aim to illustrate the scientific connotation of this thinking pattern by basing on Kidney Dominating the Reception of Qi function, combining research findings of essence of kidney organ in Chinese medicine in the past few decades and preliminary studies of this research team, and conducting research on the influences of seasonal changes on Hypothalamic–pituitary–adrenal (HPA) axis function. In Chinese medicine, Kidney Dominating the Reception of Qi function is considered to be a physiological foundation for human body to keep smooth and regular breath. Basing on this theory, researchers observed that presentations of kidney deficiency, as well as HPA axis hypofunction, are common in patients with bronchial asthma. Besides, researchers also noticed that tonifying kidney had a long-term efficacy on asthma patients and resulted in HPA axis function increases in laboratory researches. Preliminary studies of our team also verified that pineal gland, an endocrine gland being regulated by light signal, could influence neuroendocrine system and cell signaling transduction system through secreting melatonin and thus produce physiological effect. Therefore, this study will observe the regular pattern of melatonin, HPA axis and related biomolecule changes in healthy people, hamster and patients with bronchial asthma in different seasons to both provide scientific evidence for research of essence of kidney organ in Chinese medicine and make contribution to preventing respiratory diseases in the winter.

“肾应冬”是《内经》“五脏应时”理论的一个组成部分。其内涵强调肾的生理功能在通应四时变化中，与冬令时节存在特异性同步变化规律，这是中医学认识脏腑功能特性的理论思维模式。为探究此思维模式的科学内涵，本项目拟从肾主纳气功能切入，结合肾本质研究成果及本研究团队前期工作，从时令季节对下丘脑-垂体-肾上腺轴(HPA轴)功能影响的研究中做出阐释。中医理论认为肾主纳气是人体保持呼吸调匀的生理基础，研究也发现支气管哮喘患者常有肾虚征象，并伴HPA轴功能不足；补肾法能使哮喘患者获得远期疗效，使HPA轴功能提高。我们前期研究证实松果腺是受光感调节的内分泌腺，它通过分泌褪黑素，影响神经内分泌及细胞信号转导系统，产生生理效应。据此，本研究将通过观察正常人体、动物和支气管哮喘患者在不同时令季节中褪黑素、HPA轴及相关生物分子变化规律，阐释“肾应冬”生理机制的科学内涵，并为肾本质研究和呼吸疾病季节发作的防治提供依据。

“肾应冬”是《内经》“四时五藏阴阳”理论关于“五脏应时”的一个重要内容。其内涵强调肾的生理功能在通应四时变化中，与冬令时节存在特异性同步变化规律，这是中医学认识脏腑功能特性的理论思维模式。为探究此思维模式的科学内涵，本项目从肾主纳气功能切入，从时令季节对下丘脑-垂体-肾上腺轴（HPA轴）功能影响的研究中做出阐释。本研究观察了正常人体、支气管哮喘患者、正常仓鼠和摘除松果腺的仓鼠在四季血液、动物的松果腺、下丘脑、垂体、肾上腺等组织的相关生物分子的变化规律。在季节光节律调节方面，本项目研究了四季变化对松果腺褪黑素、褪黑素限速酶以及生物钟基因的影响。研究表明，松果腺褪黑素参与调节了HPA轴的神经内分泌免疫和细胞信号转导；生物钟基因Per2在调节肾上腺的季节性变化方面有重要作用。在神经内分泌免疫方面，本项目发现无论是人还是仓鼠，HPA轴上分泌的各种激素，相关的细胞免疫、体液免疫、细胞因子等免疫指标均存在着四季的波动变化，总体呈现冬季分泌降低的表现。另外，本研究还观察了松果腺对HPA轴季节性调控的细胞信号转导机制。研究结果显示：HPA轴上的G蛋白、受体、CaM、c-fos、c-jun等细胞信号转导物质也均存在四季的节律波动。由此表明，HPA轴的功能不是终年不变，而是呈现出有规律的波动，其表现与中医“五脏应时”，“肾应冬”有着较高吻合性。此外我们的研究还发现，正常人体血中的下丘脑-垂体-肾上腺轴上的激素、相关的免疫指标均呈现冬季含量最低的特点，而支气管哮喘患者以上指标的季节节律却与正常人恰恰相反，冬季含量异常地升高。这揭示了冬季HPA轴和免疫功能的过度兴奋是支气管哮喘冬春多发的重要机制，同时也说明“肾不纳气，不应冬”是支气管哮喘发病的重要原因。这一发现为今后中医药防治呼吸道疾病季节性发病提供了思路和科学依据。总之，本项目揭示了中医“肾应冬藏精，主纳气”的生物学基础，为中医学的科学性研究提供了思路和方法。