从熵变理论探讨绝经后骨质疏松症肾阳虚证与Treg/Th17介导骨免疫失衡的相关性

Human body, a non-equilibrium open system and an advanced dissipation structure, is maintained the orderly state and continuous exchange of material, energy and all kinds of information between internal and external environment by negative entropy, which would overcomes the internal positive entropy. Postmenopausal osteoporosis leads to increase the positive entropy of body and then affects the body's orderly state, because estrogen withdrawal enhances the function of Treg/Th17 mediated bone immune. It also would cause bone coupling imbalances and bone resorption of osteoclast surmounting bone formation of osteoblast. Our previous studies suggest that the syndrome element integral of postmenopausal osteoporosis kidney-yang deficiency increased significantly, which indicates that kidney-yang deficiency may be an important factor in the formation of the body's positive entropy. Therefore, the Guwei due to kidney deficiency and entropy theory will be very useful for the further research of the formation of kidney-yang deficiency. With postmenopausal osteoporosis patients as objects, we will detect Treg/Th17 cell number, mRNA, protein expression of bone immune related factors, Foxp3 and RORγt using flow cytometry, suspension array, Real time PCR and Western blot, and thus explore the relation of the entropy change in kidney deficiency and bone immune imbalance. The study will provide fundamental knowledge for the mechanism of the kidney-yang deficiency formation.

人体是一个非平衡的开放系统，又是一个高级的耗散结构，在不断与内外环境进行物质、能量等各种信息交换时，用负熵克服体内的正熵，维持机体的有序态。绝经后骨质疏松症是因雌激素水平下降引起Treg/Th17介导的骨免疫功能增强，导致骨偶联失衡，破骨细胞的骨吸收超过成骨细胞的骨形成，引发体内的正熵增加，从而影响机体的有序态。课题组前期研究发现绝经后骨质疏松症肾阳虚证素积分明显升高，提示肾阳虚可能是影响体内正熵变的重要因素之一，故本研究基于肾虚骨痿理论，以熵变理论为切入点，以绝经后骨质疏松症患者为研究对象，采用流式细胞术、悬液芯片、Real time PCR、Western blot等技术，观察绝经后骨质疏松症肾阳虚证熵变与Treg/Th17细胞数量及骨免疫相关因子、Foxp3、RORγt mRNA与蛋白表达的相关性，探讨肾阳虚证熵变与骨免疫失衡的内在关系，为阐明肾阳虚证的形成机制提供研究基础。

为了探讨绝经后骨质疏松症肾阳虚证与Treg/Th17介导骨免疫失衡的相关性，本研究基于熵变理论与证素辨证，以绝经后骨质疏松症肾阳虚证为研究对象，采用悬液芯片、流式细胞术、Real time PCR、Western blot等技术，观察了绝经后骨质疏松症肾阳虚证熵变与骨免疫失衡的内在关系。结果：(1)绝经后骨质疏松症肾阳虚证的中医病理特点是以虚为主，存在虚实夹杂、多脏腑病变，其病理基础是肾虚骨痿，为揭示熵变与绝经后骨质疏松症肾阳虚证之间的内在联系提供研究基础；(2)绝经后骨质疏松症肾阳虚证的骨免疫相关因子异常表达，引起Treg/Th17介导骨免疫失衡是绝经后骨质疏松症肾阳虚证的关键因素；(3)绝经后骨质疏松症肾阳虚证血清中E2、OPG、IGF-1含量下降，引起OPG/RANKL系统失衡，从而抑制成骨细胞的骨形成；(4)绝经后骨质疏松症肾阳虚证血清miRNA表达谱的差异分析，发现调控骨免疫、骨代谢、脂代谢的miRNA差异表达明显；(5)基于肾主骨生髓，结合中医骨伤科“筋-骨”的病机演变规律，提出“骨痿”为绝经后骨质疏松症的核心病机；(6)绝经后骨质疏松症肾虚证的舌象变化，与舌苔微环境变化密切相关。本研究初步探讨了绝经后骨质疏松症肾阳虚证与Treg/Th17介导骨免疫失衡的相关性，同时，研究结果也提示调控骨代谢与脂代谢的miRNA差异表达是影响绝经后骨质疏松症肾阳虚证形成的关键因素，为进一步从肾虚髓亏则骨髓基质干细胞成骨-成脂分化失衡揭示绝经后骨质疏松症肾阳虚证的形成机制提供了新的切入点。.本研究发表学术论文7篇，其中SCI论文2篇；培养博士研究生1名。