丝裂霉素C对滑膜成纤维细胞增殖凋亡及活化的机制研究

项目名称： 丝裂霉素C对滑膜成纤维细胞增殖凋亡及活化的机制研究

项目编号： No.81201374

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 苏长辉

作者单位： 泰山医学院

项目金额： 23万元

中文摘要： 目前对于类风湿关节炎（RA）治疗一直是困扰临床的难题。近些年研究表明滑膜成纤维细胞在RA的发病和病情发展中起的重要作用，目前抑制滑膜细胞异常增殖和血管新生成为治疗类风湿关节炎的新途径。近年研究发现丝裂霉素（MMC）在预防硬膜外瘢痕粘连有显著疗效，并初步证实其作用机制为MMC是通过诱导成纤维细胞凋亡，来预防硬膜外瘢痕粘连，并且发现MMC可抑制切口愈合过程血管新生和VEGF的表达。丝裂霉素c是否能抑制滑膜成纤维细胞增殖及活化？本课题以体外培养的RA病人滑膜成纤维细胞为研究对象，采用PCR、ELISA等研究方法观察MMC作用后对RA的滑膜成纤维细胞增殖、凋亡及其对分泌细胞因子表达转录情况进行研究，并进一步研究MMC调控滑膜成纤维细胞凋亡信号机制，以阐明丝裂霉素C对RA的治疗作用及其分子机制，为今后临床上应用丝裂霉素治疗RA提供实验依据和理论基础。

中文关键词： 丝裂霉素-c；类风湿关节炎；滑膜成纤维细胞；凋亡；线粒体途径

英文摘要： The treatment of RA has been the problem of clinical. Recent studies have demonstrated synovial fibroblast play an important role in the pathogenesis of RA, inhibiting synovial proliferation and angiogenesis becomed a method of the treatment RA. Many studies have shown that topical application of mitomycin-C can be beneficial in reducing epidural scar adhesion by inducing fibroblasts apoptosis and decrease angiogenesis via inhibiting the expression of VEGF in the process of wound healing. However, the effect of MMC on Synovial fibroblast is still unclear. In the present study, we aimed to investigate the effect of different concentration of mitomycin on cultured human synovial fibroblast of RA in vitro .synovial fibroblast proliferation and apoptosis and factor secretion were detected with PCR and ELISA ,and further investigated was performed the signal mechanism of apoptosis MMC modulated. The study attempted to investigate the effects of MMC on RA treatment and sought to determine possible mechanisms in order to provide theoretical supports to the clinical application of mitomycin

英文关键词： Mitomycin-C；Rheumatoid arthritis；Fibroblast-like synoviocytes；Apoptosis；Mitochondrial pathway