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目的制备牛Ⅱ型胶原诱导性大鼠关节炎(collagen Ⅱ-induced arthritis,CIA)模型,探讨低氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)在类风湿关节炎发病中的作用。方法50只SD大鼠,随机分为对照组与模型组。建立CIA模型,动态观察各项关节炎活动指标,于造模第21、28、35、42天取踝关节行HE染色及HIF-1α、VEGF免疫组化染色,分析两者在CIA中的相关性及与关节炎活动指标、滑膜病理学评分之间的关系。结果CIA大鼠关节滑膜层和滑膜下层均表达HIF-1α、VEGF二者呈明显正相关,r为0.75(P<0.01),第21天阳性表达量最高,随病程进展,表达逐渐下降,与滑膜病理学评分、滑膜增生评分及血管生成评分呈显著正相关,r分别为0.4、0.48、0.50(P<0.05),与炎症浸润评分无明显相关r为0.30(P<0.05)。结论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,影响类风湿性关节炎(rheumatoid arthritis,RA)的发生、发展。提示抗HIF-1α的靶向治疗有望成为RA治疗与预防的重要手段。
Objective To prepare a model of collagen Ⅱ-induced arthritis (CIA) induced by bovine type Ⅱ collagen (Collagen Ⅱ-induced arthritis) in rats, and to investigate the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor growth factor, VEGF in the pathogenesis of rheumatoid arthritis. Methods Fifty SD rats were randomly divided into control group and model group. The CIA model was set up and the indexes of arthritis activity were observed dynamically. HE and HIF-1α and VEGF immunohistochemical staining of ankle joint were performed on the 21st, 28th, 35th and 42nd days after modeling, respectively. The correlation between them in CIA Sex and the index of arthritis and synovial pathology. Results There was a positive correlation between HIF-1α and VEGF expression in both synovial and synovial layers of CIA rats (r = 0.75, P <0.01). The positive expression of HIF-1α was the highest on the 21st day , And synovial pathological score, synovial hyperplasia score and angiogenesis score was positively correlated (r = 0.4,0.48,0.50, P <0.05), but no significant correlation with inflammatory infiltration score was 0.30 (P <0.05) . Conclusion 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 rheumatoid arthritis (RA). Tip anti-HIF-1α targeted therapy is expected to become an important means of treatment and prevention of RA.