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
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。
目前临床上治疗RA常用的三大类药物有:1.改善病情药2.非甾体类抗炎药及糖皮质激素3.新的生物制剂,虽然这些药物在临床广泛应用,虽可缓解类风湿关节炎患者疾病的严重程度,减缓疾病的进展,防止继发的关节损害,但其较多副反应和高成本的治疗费用使它们在临床应用受到了限制,因此探讨RA的发病机制和新型治疗方法一直是目前RA研究的主要方向,我们课题组在前期研究中发现丝裂霉素C通过诱导成纤维细胞发生凋亡来预防硬膜外瘢痕粘连,然而丝裂霉素C对滑膜成纤维细胞作用仍然是不清楚的。因此本课题通过观察不同浓度丝裂霉素c对体外培养的RA患者滑膜成纤维细胞增殖、凋亡及其分泌细胞因子的影响,明确丝裂霉素c是否可以诱导滑膜成纤维细胞凋亡,通过检测线粒体通路凋亡蛋白的表达水平,进一步验证丝裂霉素c通过线粒体通路诱导滑膜成纤维细胞凋亡。结果表明丝裂霉素c可抑制滑膜成纤维细胞的增殖,并诱导滑膜成纤维细胞的凋亡,并呈剂量和时间依赖性,其凋亡机制可能是引起细胞内活性氧的增加从而激活线粒体凋亡途径。丝裂霉素c作为临床上常用抗肿瘤药物,本研究发现丝裂霉素c可抑制滑膜成纤维细胞的增殖并可诱导滑膜成纤维细胞的凋亡,提示其可成为一种治疗 RA 的新型药物,其对于 RA 的潜在的治疗作用属于“老药新用”的范畴,对RA有一定的治疗应用前景。
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数据更新时间:2023-05-31
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