从Ras-Raf-MEK1/2-ERK1/2信号通路探讨电针干预膝骨性关节炎软骨退变的作用机制

Ras-Raf-MEK1/2-ERK1/2 signal transduction pathway could transmit the extracellular signals into the intracellular nucleus, which results in the different protein expression spectrum change of cell and responses to many kinds of growth factor and promote mitotic, thus effectively control proliferation and apoptosis of chondrocyte. Our previous studies have shown that electroacupuncture could effectively decrease chondrocyte apoptosis and promote articular cartilage repair, suggestting that electroacupuncture may play a therapeutic role through regulating Ras-Raf-MEK1/2-ERK1/2 signal pathway. Base on these results, in the subject we investigate the effect of electroacupuncture on Ras-Raf-MEK1/2-ERK1/2 signal transduction pathway of articular cartilage, function of chondrocyte and morphological structure of articular cartilage, so as to explore the mechanism of electroacupunctures’ efficient regulation of cartilage degradation, in vivo and vitro. We may provide a new method for studying Chinese medicine prevention and treatment of osteoarthritis.

Ras-Raf-MEK1/2-ERK1/2 信号通路能将细胞外信号传递入细胞核内，引起细胞内特异蛋白的表达谱变化，能够对多种细胞生长因子和促进有丝分裂物质作出反应，从而有效调控软骨细胞的增殖与凋亡。课题前期研究表明电针能有效抑制软骨细胞凋亡，促进关节软骨修复，提示电针可能通过Ras-Raf-MEK1/2-ERK1/2 信号通路起调节作用。基于此，本课题从体内外实验探讨电针对关节软骨Ras-Raf-MEK1/2-ERK1/2 信号转导通路、软骨细胞功能及关节软骨形态结构的影响，阐明其有效调控关节软骨退变的作用机制，为中医药防治骨性关节炎提供一个新的思路。

Ras-Raf-MEK1/2-ERK1/2 信号通路能将细胞外信号传递入细胞核内，引起细胞内特异蛋白的表达谱变化，能够对多种细胞生长因子和促进有丝分裂物质作出反应，从而有效调控软骨细胞的增殖与凋亡。本课题从体内外实验探讨电针对关节软骨Ras-Raf-MEK1/2-ERK1/2信号转导通路、软骨细胞增殖与凋亡及关节软骨形态结构的影响，得出：（1）电针可通过调控Ras-Raf-MEK1/2-ERK1/2信号通路的相关指标，下调关节软骨Ras、Raf、MEK1/2、ERK1/2、C-myc、C-fos、C-jun蛋白表达，并降低滑膜组织中IL-1β含量表达，从而延缓KOA软骨退变。（2）电针干预能够减轻KOA模型大鼠软骨细胞损伤，降低膝关节部滑膜组织中TNF-α水平，下调关节软骨中Ras、Raf、MEK1/2及ERK1/2 mRNA表达，从而对KOA关节软骨发挥一定的保护作用。（3）电针治疗KOA的作用机制是通过降低软骨细胞凋亡和通过增加PGS和CollegeⅡ表达减轻关节软骨基质破坏，进而减缓关节软骨退变。（4）电针后血清可提高软骨细胞存活率，抑制TNF-α处理的软骨细胞中Ras, Raf, MEK1/2 和p-ERK1/2蛋白表达，有效抑制TNF-α介导的软骨细胞炎症。（5）电针后血清可有效抑制ERK1/2、C-myc、C-fos、C-jun mRNA表达，进而抑制TNF-α诱导的软骨细胞凋亡。以上研究结果，系统地阐明电针有效调控关节软骨退变的作用机制，为中医药防治OA提供一个新的思路。.本课题发表学术论文10篇，其中SCI源期刊收录1篇；培养硕士研究生1人。