膝骨关节炎（KOA）的发生机制和中医药防治是课题组多年的研究方向。项目组前期完成了KOA临床流行病学调研与部分机制研究，结果表明：1.多于三分之一KOA患者属于阳虚血瘀质；2.软骨细胞代谢紊乱是其主要病理表现；3.阳虚血瘀质KOA中软骨细胞的miR-424-5p/miR-582-5p表达降低。基于上述发现，提出科学假说：阳虚血瘀质的miRNA异常是导致高KOA易感性的关键环节，补肾活血方通过调控miR-424-5p和miR-582-5p降低其易感性，进而延缓或阻断KOA的病理进程。本课题拟通过体内外miRNA的过表达和敲降技术，深入探析miRNA调控与中医体质微观机制之间的相关性，进一步揭示KOA发病机制。同时应用补肾活血方干预KOA体质的偏颇状态，实现调质防病和调质防变。课题符合“健康中国”重大战略思想，通过课题的实施，践行“治未病”理念、推进中医事业发展。

The pathogenesis of knee osteoarthritis (KOA) and its prevention and treatment with Traditional Chinese Medicine (TCM) have been the key research area our team focused on for years. Previously, we unconvered the signature of clinical epidemiology and preliminary mechanism of KOA. The preliminary data demonstrates: 1. More than 1/3 of KOA patients manifest Yang deficiency and blood stasis syndrome; 2. Metabolic disorder of chondrocytes is the main pathological manifestation; 3. The miR-424-5p/miR-582-5p expression is downregulated in chondrocytes belongs to Yang deficiency and blood stasis syndrome patients. Based on the findings above, we put forward the following hypothesis: Yang deficiency and blood stasis syndrome leads to miRNA abnormity, which is the key step to high susceptibility of KOA. Bushenhuoxue recipe reduces the susceptibility by regulating miR-424-5p/miR-582-5p, contributing to postponing or stopping the pathological process of KOA.This project intends to probe into the correlation between miRNA regulation and the micro-mechanism of TCM constitution, and further reveal the pathogenesis of KOA through the overexpression of miRNA and the technique of knockdown. Besides, through the Yang-warming and blood-activating therapy, can we intervene the homeostatic disorder of constitution of KOA patients. Thus we can prevent the occurrence and development of KOA by improving the constitution. The project is in line with the important strategic thought of "healthy China", through the implementation of the project, practice the concept of "cure the disease" and promote the development of TCM.