骨关节炎是严重影响中老年人健康的常见疾病，明确本病的病机是提高中医疗效的关键。课题组初步揭示骨关节炎以肾虚为基础，肾虚髓亏，骨失所充，脑失所养，则骨代谢中枢神经调控失衡，引发软骨下骨痿，与下丘脑-软骨下骨功能网络失调有关，而在活体状态下肾虚神经环路的调控机制是亟待解决的科学问题。本研究以自然衰老与改良Hulth法建立骨关节炎肾虚证大鼠模型为研究对象：（1）从fMRI/PET活体成像，观察下丘脑-软骨下骨功能网络、代谢特征的变化，探讨肾虚神经环路动态变化的调控机制；（2）从调控下丘脑-软骨下骨的肽能神经类型，探讨肾虚神经环路的结构基础；（3）从连接下丘脑-软骨下骨信号转导的神经肽种类，探讨肾虚神经环路的调控靶点；（4）采用补肾壮筋汤干预，从方证互参角度为肾虚辨识与从肾论治提供实验依据。旨在丰富肾虚的病机理论，完善从肾论治骨关节炎的客观化研究，为建立骨关节炎中医诊疗的活体评价体系提供科学基础。

Osteoarthritis (OA) a common disease affects millions of middle-aged and elderly health and it is of great importance to understand its pathogenesis for the improvement of traditional Chinese medicine (TCM) clinical effects. Based on the former solid works, the kidney deficiency is the pathological foundation of OA. Marrow insufficiency and kidney deficiency leads to the malnutrition of bone and brain contributed to bone metabolism of the central nervous system regulation imbalance and Gu-Wei of subchondral bone that relates to the function disorder of hypothalamus-subchondral bone. However, it is a burning issues that the dynamic regulatory mechanism of kidney deficiency neural circuit in vivo. Therefore, a rat model of OA kidney deficiency using by the natural aging and modified Hulth's method will be established to do the following researches. (1) From the changes of functional connectivity networks and metabolic characteristics in hypothalamus- subchondral bone by the fMRI/PET in vivo imaging, it explores the regulation mechanism of dynamic changes of kidney deficiency neural circuit. (2) From the changes of neuropeptide neurons type in hypothalamus-subchondral bone, it explores the structural basis of kidney deficiency neural circuit. (3) From the changes of neuropeptide type in hypothalamus-subchondral bone, it explores the control targets of kidney deficiency neural circuit. (4) Using Bushen Zhuangjin Decoction treatment, it provides an experimental evidence for the syndrome differentiation and treatment by regulating kidney depended on prescriptions corresponding to syndromes. These works are to enrich the kidney deficiency pathogenesis and furtherly improve the objective research of treatment by regulating kidney providing a scientific basis for the dynamic evaluation system of TCM diagnosis and treatment in OA.