“阴阳互济”干预AMPK/mTOR通路能量代谢调控绝经后骨代谢稳态的研究

The imbalance of bone metabolism is one of the important reason of postmenopausal osteoporosis (PMOP) .The newest study found that the incidence of PMOP associated with the disorder of energy metabolism. The steady energy metabolism of AMPK/mTOR signaling pathway played an important role in the regulation and the control, which was a focal point of factors. TCM consider that the fundamental cause of PMOP is the kidney deficiency. Our previous studies have found that based on the yin and yang balance of kidney, both the Zuogui Pill and Yougui Pill can pass through the TGF-β/Smad-ERK signaling pathway and effectively prevent PMOP, in differentiation and balance system of interventing osteogenesis and adipogenesis , there are the yin and yang regulating factors. The project assumes that “ based on the principle that mutual aid of yin and yang in the kidneys, both the Zuogui Pill and Yougui Pill, by intervening in AMPK/mTOR signaling pathway of energy metabolism, can effectively regulate and control the steady state of bone metabolism ". In order to confirm the hypothesis, with ovariectomized PMOP model and under the condition of PMOP state, it is the object of study that, in vitro , osteogenesis, adipogenesis and broken bone cells are induced with bone marrow and on the AMPK/mTOR signaling pathway, by using varieties of molecular biology techniques, the hypohesis is verified through the whole--organ--cells-- molecular level, which can delve into the molecular mechanism of yin and yang balance( mutual aid of yin and yang), to provide new and rich ideas for the treatment of PMOP .

骨代谢稳态失衡是绝经后骨质疏松症（PMOP）发生的重要原因之一，最新研究发现PMOP的发生与能量代谢紊乱有关，AMPK/mTOR信号通路能量代谢对骨代谢稳态发挥重要的调控作用，是多种因素的汇聚点之一。中医学认为肾虚是PMOP发生的根本原因，我们前期研究发现基于肾之“阴阳互济”的左归丸与右归丸均能通过TGF-β/Smad-ERK信号途径有效防治PMOP，在干预成骨与成脂分化平衡体系内，存在阴阳属性的调节因素。本项目假设“基于肾之‘阴阳互济’法则的左归丸与右归丸可通过干预AMPK/mTOR信号通路能量代谢而有效调控PMOP骨代谢稳态”，为证实假说，拟以去卵巢PMOP模型和PMOP状态下的骨髓体外诱导的成骨、成脂、破骨细胞为研究对象，以AMPK/mTOR信号通路为切入点，运用多种分子生物学技术，从整体-器官-细胞-分子水平验证假说，深入探讨阴阳互济的分子机制，为丰富PMOP治法理论提供新思路。

骨代谢稳态失衡是绝经后骨质疏松症（PMOP）发生的重要原因之一，最新研究发现PMOP的发生与能量代谢紊乱有关，AMPK/mTOR信号通路能量代谢对骨代谢稳态发挥重要的调控作用，是多种因素的汇聚点之一。中医学认为肾虚是PMOP发生的根本原因，本项目以去卵巢建立绝经后骨质疏松症（PMOP）模型，并以PMOP模型和PMOP状态下BMSCs为研究对象，以AMPK/mTOR信号通路为切入点，运用多种分子生物学技术，从整体-器官-细胞-分子水平研究肾之阴阳互济中药调控PMOP能量代谢干预骨代谢稳态的机制，研究发现PMOP的发生伴随着能量代谢紊乱，AMPK/mTOR信号通路介导了PMOP的骨代谢稳态；左归丸与右归丸均能有效防治PMOP，有助于改善能量代谢失调、恢复骨代谢稳态平衡，且可干预AMPK/mTOR信号通路；但在骨脂平衡、成骨破骨平衡方面，左归丸与右归丸作用有所不同，“阳中求阴”之左归丸偏于调控骨形成，而“阴中求阳”之右归丸偏于调控骨吸收及成脂以及能量代谢，这些发现无疑为临床预防PMOP的发生及治疗提供了好的思路和干预靶点，同时也为进一步揭示肾之“阴阳互济”的科学内涵提供新的思路与方法，为丰富PMOP治法理论提供新的思路与方法。