通痹灵抑制佐剂性关节炎及巨噬细胞分泌环氧化酶影响的研究

【作者】 陈立洳；

【导师】 黄仰模；

【作者基本信息】 广州中医药大学 ， 中医临床基础， 2005， 硕士

【摘要】 类风湿关节炎(Rheumatoid arthritis, RA)是一种病因不明的自身免疫性疾病,多见于中年女性,我国的患病率约为0.32%～0.36%。主要表现为对称性、慢性、进行性多关节炎。关节滑膜的慢性炎症、增生形成血管翳,侵犯关节软骨、软骨下骨、韧带和肌腱等,造成关节软骨、骨和关节囊破坏,最终导致关节畸形和功能丧失。RA的特点是反复发作,病情缠绵难愈。近年来,西医学存RA发病机制及病理变化研究等方面取得了明显进步,在治疗方面,新药物新疗法层出不穷,但至今仍然缺乏理想的疗法和药物,特别是在改善和阻止RA病情发展方面仍进展不大。因此,研究和寻找RA治疗的有效方法药物,是医学工作者紧迫的任务。 单核巨噬细胞在RA中扮演着重要的角色,一方面,激活的单核巨噬细胞产生广泛大量的炎性介质,包括有RA发病的中心罪犯之称的白细胞介素-1(IL-1)和肿瘤坏死因子-α(TNF-α)以及其他多种炎性因子;另一方面,单核巨噬细胞又作为抗原递呈细胞摄取外来抗原,加工后与人类的主要组织相容性复何物(HLA)分子结合,一并呈递和共同刺激淋巴细胞,进行免疫应答。因此,有人认为,是激活的单核巨噬细胞控制着RA的滑膜炎发展。因此,研究药物对RA单核巨噬细胞的作用可以为控制RA滑膜炎提供良好的依据。 通痹灵是临床治疗RA的有效纯中药复方制剂,来源于《金匮要略·中风历节病》篇中的桂枝芍药知母汤,经加减变化而制成中成药,应用于临床多年,取得较好的疗效,既往的实验研究亦证实对慢性RA关节炎模型——CIA大鼠,通痹灵能抑制滑膜炎,减轻软骨和骨质破坏,并且无明显毒副作用。 通痹灵总碱是采用化学方法运用有机溶剂从通痹灵复方中提取的通痹灵有效部位,既往研究表明通痹灵总碱能抑制CIA大鼠滑膜成纤维细胞增殖。 本研究在既往研究的基础上,采用公认的急性RA动物模型——AA大鼠,研究通痹灵总碱对急性关节炎的药效;药效机理研究方面,采用体外培养人类单核巨噬细胞,研究通痹灵总碱对脂多糖(LPS)刺激下的单核细胞分泌环氧化酶影响的作用。拟阐明通痹灵总碱抗炎的部分机理。 药效研究发现,通痹灵总碱能减轻AA大鼠的足肿胀度,减少足肿计分。病理研究显示,通痹灵总碱能有效抑制AA大鼠中性粒细胞浸润、淋巴细胞浸润、关节纤维化、关节血管翳的增生,从而减轻关节炎症反应。 对药效机理的研究显示,通痹灵总碱可以抑制体外培养的巨噬细胞产生环氧化酶,此作用是通过顯著性抑制环氧化酶—2(COX-2)来实现的,具有类似于特异性COX-2抑制剂的作用,也很好的解释了复方中药制剂通痹灵抗炎而无胃肠道副作用的机理。为通痹灵在临床的推广应用提供了部分实验依据。更多还原

【Abstract】 RA is one kind of autoimmune disease which the cause is still unknown. It is mainlyfound in female. The sickness rate of RA is about 0.32-0.36% in China. The mainclinical manifestation is chronic, systemic, inflammatory disorder in which an erosivesymmetric joint.In the early months of RA, edema, angiogenesis, hyperplasia of synovial lining, andinflammatory infiltrate are already present. Once the disease enters a more chronicphase, massive hyperplasia, mainly of type A synovial cells, and subintimalmononuclear cell infiltration are prominent. The synovium of RA assume theappearance of a reactive lymph node because of the extensive infiltration by plasmacells, macrophages, and lymphocytes in the form of large lymphoid follicles.One characteristic feature of RA is the invasion of and damage to cartilage, bone andtendons by an infiltrating inflammatory synovial tissue mass called the pannus.Mononuclear leukocyte plays an important role in LA. The active mononuclearleukocyte can produce lots of inflammatory factors including the main crimricalfactor IL-1 and ITNF-a. on the other side, as the antigen presented cell it can uptakingantigen, stimulate lymphocyte, so it is said that mononuclear leukocyte control thedeveloping of RA synovitis. It is not unreasonable to suggest that suppress of thefunction of mononuclear leukocyte can inhibit synovitis of RA.TongBiLing (TBL) is a compound prescription created by professor Chenjifan. Itderives from the Decoction Cinnamomi, Paeoniae and Anemarrhenae whichextracting from synopsis of Golden Cabinet. Some of TBL’s mechanism have beenverified by AA mouse and CIA mouse.In our study, to further elucidate the anti-synovitis effect of TBL on AA. We useadjusted arthritis rat as animal model.Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune, inflammatorydisorder , which is occurring in about 0.32% - 0.30% of population in our country,and the course of RA is still known.The main features of RA are an inflamed synovial lining of the joint spaces,characterized by abnormal angiogtnesis, marked leukocyte infiltration and synovialceuproliferation. An inflammatory pannus eventually invades and destroys theunderlying cartilage and bone, leading to severe pain and impairment of mobility. Themajority of the manifectations of RA-inflammation, joint swelling, bone and cartilagedegeneration, and pain-can be attributed to ten pannus-derived inflammatory.更多还原