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建立Wistar大鼠Ⅱ型胶原诱导性关节炎(CIA)模型,探讨低氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)在CIA中的表达,为类风湿关节炎的发病机制及治疗前景提供线索。采用50只Wistar大鼠,随机分为对照组与模型组,将牛Ⅱ型胶原与福氏不完全佐剂乳化混匀作为免疫混合物,尾根部皮内注射,建立CIA模型。于造模第21、28、35、42天取踝关节和滑膜组织行HE染色及免疫组化染色,动态观察各项关节炎活动指标和检测HIF-1α和VEGF在CIA关节炎中的表达,并分析两者在CIA中的相关性及HIF-1α与滑膜病理学评分之间的关系。组织形态学和影像学结果显示,CIA大鼠的滑膜组织、关节软骨及骨组织均呈典型的关节炎病变;免疫组化结果显示CIA大鼠关节滑膜层和滑膜下层均表达HIF-1α和VEGF,第21天阳性表达量最高,随病程进展,表达逐渐下降;统计学分析表明HIF-1α和VEGF的表达水平呈正相关(r=0.75,P<0.01),HIF-1α的表达水平与滑膜病理学评分和血管生成评分呈正相关(r_1=0.48,r_2=0.5,P<0.05)。以上结果提示HIF-1α可能通过调控一系列下游靶基因,如VEGF等,促进滑膜增生及血管生成,影响RA的发生与发展。
To establish the type Ⅱ collagen-induced arthritis (CIA) model in Wistar rats and investigate the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in CIA and the pathogenesis of rheumatoid arthritis And treatment prospects. Fifty Wistar rats were randomly divided into control group and model group. The bovine type Ⅱ collagen and incomplete incomplete adjuvant were emulsified and mixed as the immunological mixture. The tail root was injected intradermally to establish CIA model. At the 21st, 28th, 35th, and 42th day after modeling, the ankle joint and synovial tissue were harvested for HE staining and immunohistochemical staining. The indexes of arthritis activity and the expression of HIF-1α and VEGF in CIA arthritis were observed dynamically , And analyzed the correlation between the two in CIA and the relationship between HIF-1α and synovial pathology score. Histomorphology and imaging results showed that the synovial tissue, articular cartilage and bone tissue of CIA rats showed typical arthritic lesions. Immunohistochemistry showed that the expression of HIF- The expression of HIF-1α and VEGF was positively correlated with the expression of VEGF (r = 0.75, P <0.01), and the expression of HIF-1α It was positively correlated with synovial pathology score and angiogenesis score (r = 0.48, r = 0.5, P <0.05). The above results suggest that HIF-1α may promote synovial hyperplasia and angiogenesis by regulating a series of downstream target genes, such as VEGF, affecting the occurrence and development of RA.