膝骨关节炎(OA)属中医“骨痹”范畴，软骨细胞减少是OA最主要的病理过程。最近研究表明生长激素释放促分泌素受体的内源性配体Ghrelin是参与软骨合成的重要因子，而我们前期发现Ghrelin与OA严重程度呈负相关，是OA进展的保护因子，但Ghrelin被何种因素调控尚不明确。脾肾亏虚是引发OA的重要原因，而表观遗传效应与“脾”“肾”功能密切相关，其中RNA调控是表观遗传的重要内容。本研究拟制造SD大鼠膝OA模型，从表观遗传中的CircRNA-miRNA(ceRNA，竞争性内源RNA)机制着眼，探讨OA发生时软骨CircRNA-miRNA 表达差异情况，筛选针对Ghrelin的CircRNA-miRNA，并进一步探讨“肾腧”“足三里”艾灸血清“补益脾肾”法是否可以通过调控筛选的CircRNA-miRNA促进Ghrelin表达，保护OA软骨细胞，为艾灸防治膝OA奠定深层次的理论基础。

Knee osteoarthritis belongs to “Gu Bi” in traditional Chinese medicine。The chondrocytes reduction is the main pathophysiological process of OA. Ghrelin,the endogenous ligand of growth hormone secretagogue receptor，has been identified as an important role on participating in cartilage synthesis. In our previous study,we found Ghrelin was negatively related to disease severity in OA and may act as a protective factor of OA. However, what regulates ghrelin remains unclear.The deficiencies of “spleen” and “kidney” are important factors to cause OA. Epigenetic effect is associated with the function of “spleen” and “kidney”,and RNA regulation is one of the most important topics in epigenetics.Therefore,the current study is carried out to establish the SD rat OA model,based on the CircRNA-miRNA(ceRNA,competing endogenous RNAs )mechanism in epigenetics,to explore the distinction expression of miRNA-CircRNA during OA process, screening CircRNA-miRNA interaction pairs targeting Ghrelin.We further explore whether “Shen Shu””Zu San Li”moxibution serum “Tonifying spleen and kidney”method could promote ghrelin expression through our screened CircRNA-miRNA interaction pair,thus providing profounding theoretical basis for moxibution preventing and treating knee OA.