基于“骨肉不相亲”理论研究熟地-黄芪配伍干预“骨-肌-串扰” 治疗绝经后骨质疏松症的作用机制

Postmenopausal osteoporosis is a common disease that threatens the health of middle-aged and elderly women. Chinese medicines have some advantages in the treatment of postmenopausal osteoporosis, such as small side effects and improvement of patients’ systemic symptoms. Based on the pathogenesis of the bones and bones, the Chinese medicine practitioners follow the principles of nourishing the kidney-essence and invigorating the spleen and blood. The kidney is in charge of the bone, and the spleen is in charge of the muscles. The spleen and kidney are closely related, which corresponds to the coordination of bones and muscles. The biochemical ‘crosstalk’ between bone and muscle is closely related to the pathogenesis of PMOP, and the PI3K/Akt/mTOR pathway is the key pathway for ‘crosstalk’ between bone and muscle. Based on the correlation between ‘bone-muscle-crosstalk’ and TCM ‘disharmony between bone and muscle theory’, this study used the method of whole bone marrow adherence, RT-PCR and Western Blot to study the effects of the combination of Rehmannia and Radix Astragali on the metabolism and proliferation of bone and skeletal muscle of PMOP rats. It also elucidated its regulation of PI3K/Akt/mTOR signaling pathway-related factors to reveal its target for the treatment of PMOP.And to clarify its regulation of PI3K/Akt/mTOR signaling pathway-related factors, to reveal its target for the treatment of PMOP by intervening ‘bone-muscle-crosstalk’.

绝经后骨质疏松症是威胁中老年妇女健康的一种常见疾病，中医药治疗该病具有副作用小且能改善患者全身症状等优势。基于骨痿“骨肉不相亲”之病机，中医多遵循补肾填精、健脾养血为主的治疗原则。肾主骨，脾主肌肉，肾脾二脏的相资互用，对应于骨骼与肌肉的相互协调。骨与肉之间存在的生化“串扰”与PMOP的发病密切相关，其中PI3K/Akt/mTOR通路是骨与肉之间“串扰”作用的关键通路。基于“骨-肌-串扰”与中医“骨肉不相亲理论”的相关性，本课题以熟地-黄芪药对为研究对象，采用全骨髓贴壁分离法、RT-PCR、Western Blot等方法，研究熟地-黄芪配伍给药后对PMOP大鼠骨组织和骨骼肌的代谢及增殖分化水平的影响，并阐明其对PI3K/Akt/mTOR信号通路相关因子的调节作用，以揭示“熟地-黄芪”配伍干扰“骨-肌-串扰”治疗PMOP的作用靶点。

绝经后骨质疏松症（PMOP）是绝经后妇女的常见病及多发病，中医治疗多遵循补肾填精、健脾养血为主的原则。项目组前期研究发现熟地配伍黄芪治疗PMOP具有较好的治疗效果，但其作用机制尚不明确。本项目研究发现，熟地-黄芪配伍能明显提高大鼠腰椎和胫骨的骨密度，通过调节血清骨代谢指标可促进骨形成和骨骼肌生长，并能明显改善骨质疏松大鼠的骨组织结构，缓解大鼠肌组织的萎缩状态；采用全骨髓贴壁法分离培养大鼠骨髓间充质干细胞，通过体外实验研究发现熟地-黄芪配伍可促进BMSCs矿化结节的生成，提高其成骨分化能力，并抑制大鼠BMSCs向脂肪细胞分化。研究结果表明，熟地-黄芪配伍治疗PMOP的作用机制可能与激活PI3K/Akt/mTOR信号通路有关。通过本项目的研究，揭示了熟地-黄芪配伍治疗PMOP的作用靶点，为中药配伍研究提供了新思路。