滑膜成纤维细胞在类风湿性关节炎中的作用及中药干预研究进展

Effect of Synovial Fibroblasts in Rheumatoid Arthritis and Intervention of Chinese Medicine:A Review

类风湿性关节炎(RA)是一种常见的自身免疫性疾病,滑膜组织的过度增生和破骨细胞性骨吸收是引起RA发生骨、关节破坏的两大主要原因。RA滑膜成纤维细胞(RA-FLS)是RA滑膜组织中最主要的细胞之一,其生长特性的改变及凋亡抑制导致滑膜组织增生,激发炎症反应,破坏关节结构及导致关节功能障碍。因此,调控RA-FLS的异常增殖和促凋亡能够干预RA发病进程。目前有很多中药及中药单体成分对RA-FLS过度增殖及促凋亡方面的研究。鉴于此,本文通过查阅大量文献资料,对RA-FLS在RA中的作用及中药单体和复方通过调控RA-FLS来干预RA的相关研究进展进行了综述,结果表明,单体成分包括萜类、黄酮类、生物碱类、蒽醌类及其他类。虽然他们的类型不相同,但通过不同的途径最终达到能够有效地干预RA。如通过抑制炎性细胞因子的分泌,抑制软骨细胞及破骨细胞的生成从而防治骨、软骨的破坏,和上调Fas/FasL、核转录因子-κB(NF-κB)、JAK/信号传导及转录激活因子(STAT)、p38丝裂原活化蛋白激酶(p38 MAPK)等信号通路中的促凋亡基因B细胞淋巴瘤-2(Bcl-2)相关X蛋白(Bax)、胱天蛋白酶(Caspase)及下调抑制凋亡基因Bcl-XL、Bcl-2的水平而实现细胞凋亡,以及降低RA-FLS自噬蛋白微管相关蛋白1轻链3Ⅱ(LC3Ⅱ)/LC3Ⅰ、Beclin-1蛋白表达水平而实现抑制RA-FLS增殖。虽然他们的分子作用机制和靶点不相同但都起到了相应的作用,以上研究结果为阐明中医药的多成分、多靶点治疗RA提供了科学依据。

Rheumatoid arthritis(RA)is a common autoimmune disease. Excessive hyperplasia of synovial tissues and osteoclastic bone absorption are two main causes of bone and joint destruction in RA.Synovial fibroblasts in RA(RA-FLS)are important cells in the synovial tissues of RA. The changes in their growth characteristics and inhibition of apoptosis lead to the proliferation of synovial tissues, stimulate inflammatory reactions,damage joint structure,and result in joint dysfunction. Therefore,regulating abnormal proliferation and promoting apoptosis of RA-FLS can interfere with the pathogenesis of RA. At present,there are many studies on the effect of Chinese medicine and its monomer components on the excessive proliferation and apoptosis of RA-FLS. The present study reviewed the effect of RA-FLS in RA and the intervention of Chinese medicinal monomers and compounds by regulating RA-FLS. The results showed that monomer components mainly included terpenoids, flavonoids, alkaloids, and anthraquinones. Despite different types, they can effectively intervene in RA through different approaches. For instance,they can prevent bone and cartilage injury by inhibiting the secretion of inflammatory cytokines and inhibiting the generation of chondrocytes and osteoclasts. They can achieve apoptosis by up-regulating the pro-apoptotic genes B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),and cysteinyl aspartate-specific protease(Caspase)in the Fas/FasL,nuclear factor-κB(NF-κB),Janus kinase(JAK)/signal transducer and activator of transcription protein(STAT),and p38 mitogen-activated protein kinase(p38 MAPK)signaling pathways,and down-regulating the anti-apoptotic genes Bcl-xl and Bcl-2. They can also inhibit the proliferation of RA-FLS by inhibiting the protein expression of microtubule-associated protein 1 light chain 3 Ⅱ(LC3 Ⅱ )/LC3 Ⅰ and Beclin-1. Although their molecular mechanisms of action and targets are different,they all exert corresponding roles. The above research results provide a scientific basis for elucidating the multi-component and multi-target characteristics of Chinese medicine in the treatment of RA.