CIA 模型制备及HIF-1α, VEGF 在其中的表达与意义.docVIP

CIA模型制备及HIF-1α、VEGF在其中的表达与意义 王雯1 陈森洲2◆ 王险峰2 侯巧燕1 骆耐香2 李莎莎1 （1.桂林医学院病理科，桂林 541001 2.桂林医学院微生物学与免疫学教研室，桂林 541004） 摘要：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(HIF-1α)、血管内皮生长因子(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、VEGFCIA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，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，与炎症浸润评分无明显相关。结论 Ⅱ型胶原可成功诱导大鼠关节炎模型。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、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。 关键词：类风湿关节炎；Ⅱ型胶原诱导性关节炎；低氧诱导因子-1α；血管内皮生长因子；滑膜 Expression and significance of HIF-1α and VEGF in collagen Ⅱ induced arthritis WANG Wen, CHEN Sen-zou，WANG Xian-fen( Department of microbiol and immunology, Guilin medical college, Guilin 541004, China ) Abstract：Objective To establish the bovine collagenⅡ(CⅡ)-induced arthritis(CIA) rat model, investigate the role of hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor (VEGF) in the pathogenesis of rheumatoid arthritis(RA). Methods 50 SD rats were randomly divided into normal group and model group. The model group was subjected to CIA. The arthritis activity, pathological changes and expression of HIF-1α and VEGF on synovium at different time were observed through HE and immunohistochemistry staining. The correlations of HIF-1α and VEGF expression with the CIA arthritis activity indexes and pathological scores were analyzed. Conclusion HIF-1α and VEGF expession were found on both lining and sublining area of synovium in CIA. The results of immunohischemistry test showed that the expression of HIF-1α and VEGF in synovial membrane was strongest on the 21st day, descent gradually with the prolonged disease course. The expression of HIF-1α and VEGF correlated significantly with total pathological score, synovial hyperplasia score and angiogenesis score, but not with inflammation score. Results Type Ⅱ collagne can induce an animal model of arthritis in rats successfu