从TβRII调控的TGF-β/Smad信号通路受到抑制引起的炎症反应增强探讨膝骨关节炎肝肾亏虚证的科学内涵

肝肾亏虚证是膝骨关节炎代表性证候，炎症反应引起软骨损伤是该病核心病理机制。课题组发现①膝骨关节炎肝肾亏虚证患者炎症因子浓度升高，与证候严重程度呈正相关；②该病-证患者Smad2浓度下降；③补肾强骨中药能作用于TGF-β/Smad信号通路发挥抗炎效应，对于软骨损伤进行修复。该通路受TβRII自身磷酸化调控，受到抑制后出现Smad2浓度下降，炎症反应增强，与①②结论一致，说明该通路在该病-证状态下的关键地位。然而，该病-证中TβRII自身磷酸化表达出现什么样的特异性变化，此变化对TGF-β/Smad信号通路的具体作用靶点，调控作用与炎症反应之间的关系尚不明确。本项目应用患者关节液刺激软骨细胞，明确该病-证引起TβRII自身磷酸化表达下降的表观遗传学基础、分子生物学调控机制及核心作用特点；进一步解析TβRII、通路产物浓度与炎症反应水平的相关性；药证相关，应用柚皮苷反证；揭示该病-证的科学内涵。

Liver-kidney deficiency syndrome is a representative of knee osteoarthritis, and cartilage injury caused by inflammatory response is the core pathological mechanism of the disease. The research group found that ① the concentration of inflammatory factors increased in patients with knee osteoarthritis of liver-kidney deficiency syndrome, which was positively correlated with the severity of syndrome; ② the concentration of Smad2 decreased in patients with the disease-syndrome; ③ traditional Chinese medicine for tonifying kidney and strengthening bone could exert anti-inflammatory effect on TGF-β / Smad signaling pathway and repair cartilage injury. This pathway was regulated by the autophosphorylation of TβRII. After the pathway was suppressed, the concentration of Smad2 decreased and the inflammatory response increased, which was consistent with the conclusion of ①②, indicating that the pathway played a key role in the disease-syndrome state. However, the specific changes of TβRII autophosphorylation expression, the specific targets of this change on TGF-β /Smad signaling pathway and the relationship between regulatory effect and inflammatory response were not clear in the disease-syndrome. In this project, synovial fluid of patients was used to stimulate chondrocytes to clarify the epigenetic basis, molecular biological regulation mechanism and core characteristics of the decrease of TβRII autophosphorylation caused by the disease-syndrome. To further analyze the correlation between TβRII, pathway product concentration and inflammatory response level. Drug indications related, the application of naringin to counterevidence. Revealed the scientific connotation of the disease - syndrome.