【摘要】 背景:缺氧诱导因子在类风湿关节炎中的作用已经得到广泛证实,而作为缺氧诱导因子重要的调节因子脯氨酸羟化酶及希佩尔林道肿瘤抑制蛋白(von-Hippel-Lindau tumor suppressor protein,pVHL)是否在类风湿关节炎中作用国内外尚无明确报道。目的:分析类风湿关节炎和骨关节炎滑膜组织中脯氨酸羟化酶和pVHL的表达及其相互关系,探讨低氧信号蛋白在类风湿关节炎中的影响机制。方法:取行膝关节置换的类风湿关节炎患者滑膜组织11例,并取行膝关节置换的骨关节炎患者滑膜组织20例做对照。研究的实施符合青海大学附属医院医院对研究的相关伦理要求,患者对治疗过程及试验过程完全知情同意。采用免疫组织化学Envision二步法,检测2组滑膜组织中脯氨酸羟化酶1,2,3及p VHL的表达。结果与结论:①免疫组织化学结果显示,脯氨酸羟化酶1,2,3及p VHL在类风湿关节炎和骨关节炎滑膜组织中均有表达;脯氨酸羟化酶1在类风湿关节炎滑膜组织中的表达显著低于骨关节炎组(P <0.01),脯氨酸羟化酶2在类风湿关节炎滑膜组织中的表达显著高于骨关节炎组(P <0.05);脯氨酸羟化酶3、pVHL的表达2组差异无显著性意义(P> 0.05);②相关分析显示,类风湿关节炎组脯氨酸羟化酶2与脯氨酸羟化酶3(r_s=-0.875,P <0.01),脯氨酸羟化酶1与红细胞分布宽度标准差(r_s=-0.374,P <0.03),脯氨酸羟化酶2与血红蛋白(r_s=-0.457,P <0.01),脯氨酸羟化酶3与红细胞分布宽度标准差(r_s=-0.363,P <0.04)均呈负相关;脯氨酸羟化酶2与嗜酸性粒细胞(r_s=0.363,P <0.04),脯氨酸羟化酶2与球蛋白(r_s=0.405,P <0.02),均呈正相关;③类风湿关节炎组类风湿因子、C-反应蛋白、血清淀粉样蛋白A、球蛋白检测值均显著高于骨关节炎组(P <0.05);④结果说明,脯氨酸羟化酶1和脯氨酸羟化酶2与类风湿关节炎的发生、发展密切相关,抑制脯氨酸羟化酶2的表达及激活脯氨酸羟化酶1的表达可能在类风湿关节炎滑膜组织的病理改变中起到重要保护作用,或可为类风湿关节炎发生的分子生物学途径及临床之中提供有针对性的治疗措施。更多还原

【Abstract】 BACKGROUND: It is widely recognized that hypoxia-inducible factor plays a role in rheumatoid arthritis. As the key factors of hypoxia-inducible factors, whether prolyl hydroxylase and von-Hippel-Lindau tumor suppressor protein(pVHL) participate in rheumatoid arthritis still remains unknown.OBJECTIVE: To investigate the relationship between prolyl hydroxylase and pVHL in the synovial tissues of rheumatoid arthritis and osteoarthritis, and to explore the underling mechanism.METHODS: Synovial tissues were removed from 11 patients with rheumatoid arthritis undergoing knee arthroplasty, and synovial tissues from 20 patients with osteoarthritis undergoing knee arthroplasty were as controls. The study was approved by the Ethics Committee of Affiliated Hospital of Qinghai University, and the patients signed the informed consents. The expression levels of prolyl hydroxylases 1, 2 and 3, and pVHL in the synovial tissues were detected by immunohistochemical EnVision two-step method.RESULTS AND CONCLUSION:(1) All of the prolyl hydroxylases 1, 2 and 3, and pVHL were positive in the two groups. Prolyl hydroxylase 1 was significantly lower in rheumatoid arthritis patients than in osteoarthritis patients(P < 0.01). The expression level of prolyl hydroxylase 2 in rheumatoid arthritis patients was significantly higher than those in synovial tissues of osteoarthritis(P < 0.05). There was no significant difference in the expression of hydroxylase 3 and pVHL between two groups(P > 0.05).(2) The analysis of Spearman rank correlation showed that hydroxylases 2 and 3(r_s=-0.875, P < 0.01), hydroxylase 1 and red blood cell distribution width-standard deviation(r_s=-0.374, P < 0.03), hydroxylase 2 and hemoglobin(r_s=-0.457, P < 0.01), hydroxylase 3 and red blood cell distribution width-standard deviation(r_s=-0.363, P < 0.04) were negatively correlated respectively, while there were positive correlation between hydroxylase 2 and eosinophil(r_s=0.363, P < 0.04), hydroxylase 2 and hemoglobin(r_s=0.405, P < 0.02), respectively.(3) Rheumatoid factor, C-reactive protein, serum amyloid A, and globulin were significantly higher in serum of rheumatoid arthritis patients than in those of the osteoarthritis patients(P < 0.05).(4) These results indicate that the changes of hydroxylases 1 and 2 in synovial tissues of rheumatoid arthritis patients might be involved in the pathogenesis of this disease, which can help us understand a way of molecular biology for the occurrence of rheumatoid arthritis.更多还原