【作者】 钱玉中；

【导师】 张国恩；

【作者基本信息】 河北医科大学 ， 中西医结合临床， 2005， 硕士

【摘要】 目的:类风湿关节炎(rheumatoid arthritis ,RA)是最常见的风湿病之一,是一种反复发作以对称性多关节炎,关节慢性进行性破坏为特征的自身免疫性疾病。其病因及发病机制未明,但其主要的病理环节基本清楚,即免疫功能失常表现以T 淋巴细胞为主的大量炎细胞浸润、滑膜衬里层细胞增殖、血管新生及血管翳形成。活化增殖的淋巴细胞和滑膜细胞的过度增生导致RA 关节炎症和软骨及骨破坏。细胞因子是滑膜炎症反应和免疫应答的重要介质,具有促炎、抑炎及正负反馈的免疫调节作用,参与滑膜病理变化的全过程。RA 另一重要的病理改变是关节软骨及骨组织的破坏,软骨及骨组织的破坏在RA 发病的早期即已开始,软骨破坏与再生的过程也都是在细胞因子的参与下进行的。痹康饮合剂是治疗类风湿性关节炎活动期的有效中药,临床运用治疗RA取得良好疗效。本实验以CIA 大鼠为模型,观察痹康饮合剂对滑膜组织和软骨病理学及相关细胞因子表达水平的变化,探讨痹康饮合剂在RA 治疗中的抗炎及免疫调节机理,为推广痹康饮合剂提供实验依据。方法:1 建立II 胶原诱导关节炎大鼠模型;2 测量大鼠足肿胀度,计算肿胀率及关节炎指数(AI);3 通过光镜观察实验大鼠滑膜和软骨中组织病理学形态结构的变化。4 采用免疫组化染色方法,评价造模后痹康饮合剂早期给药治更多还原

【Abstract】 Objective: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory disorder and progressive joint destruction. Moreover, vascular endothelial growth factor (VEGF) is related to the hyperplasia of blood vessel. Treatment of rheumatoid arthritis (RA) with Bikangyin Mixture (BKY) decoction is highly clinically effective. This study was undertaken to investigate the clinical efficacy of Bikangyin decoction to the patient in active stage of rheumatoid arthritis (RA), explore the precise mechanism of the action of BKY in RA, and provide the experimental evidence for its application. Methods: 1 Arthritis model in rats induced by type II collagen was established. 2 The feet swelling degrees of rats were measured, and then calculated the swelling rate. 3. After a short-term treatment, the synovial histopathology of rats was observed with optical microscope respectively. 4 Immuno -histochemistry techniques have been used to detect T-cell subsets, cytokines TNF-α、TGF-β、MMP3、TIMP1 and VEGF in synovial tissue (synovial membrane) of CIA rats. The above results were analyzed with image analysis system. Result: 1 The CIA rats had obvious and persistent arthrocele, but the articulus had no clinical manifestation of red glow. The histopothology of arthral tissue showed lymphocyte infiltrating and liner hyperplasy in the synovial membrane, neovascularity and pannus’forming. 2 The BKY decoction of high dose had more obvious effects than low-dose BKY decoction or MTX on reducing foot swelling or arthritis index. 3 There were a great quantity of lymphocyte infiltrating and synoviocyte hyperplasy in the model group rats’synovial tissue, but the situation was well in the BKY decoction high-dose group. 4 The number of chondrocytes with positive TNF-αexpression was lower and the chondrocytes were stained lighter in normal group than those in model group and low-dose MTX group(P <0.01). The expression of TNF-αin high-dose and low-dose TBL groups and high-dose RTW group was similar to that in normal group and more obvious than that in high-dose and low-dose MTX group(P<0.05) and model group(P<0.01).The expression of TGF-βin normal group was more obvious than that in high-dose and low-dose RTW groups(P<0.05).The expressions of TNF-αand TGF-βin high-dose and low-dose TBL groups were similar to those in normal group and different from those in model group(P<0.01). 5 The expression of VEGF in high-dose group was lower than that in normal group or other group (P<0.05). 6 In the high-dose group, the expression of MMP3 dropped, but the expression of TIMP1 rose. 7 The X-ray imaging changes of CIA rats: The ratsof model group had soft tissue swelling、destruction of bone and vague joint space. That situation changed a lot after treating with high dose BKY decoction, but the changes were little in the low-dose group or MTX group. Conclusion: The detection result of cytokine by immunohitochemistry showed that Bikangyin decoction has obvious effect to arthritis induced by type II collagen. The mechanism of its action are mainly: First, it can reduce the expression of TNF-αand raise the expression of TGF-β, and then keep the balance of Th1/Th2、control the hyperplasy of synoviocyte、lighten arthral inflammatory、prevent the cartilage or bone from destruction. Second, it can inhibit the generation of VEGF, and so inhibit vascular proliferation、pannus forming; Reduce vasopermeability; stop the excess hyperplasy of synoviocyte; prevent or lessen the destruction of bone. Lastly, it can inhibit the excess expression of MMP3 and adjust the balance of MMP3/TIMP1, and so relief the symptom of arthritis and the destruction of cartilage.更多还原