益肾蠲痹丸对Ⅱ型胶原致关节炎大鼠踝关节组织病理改变的影响及其机制研究

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目的观察益肾蠲痹丸对II型胶原诱导性关节炎(CIA)大鼠的治疗作用及对踝关节组织病理改变的影响,并探讨益肾蠲痹丸治疗类风湿性关节炎(RA)与血管内皮生长因子(VEGF)的相关性。方法通过建立CIA大鼠模型,观察益肾蠲痹丸对CIA大鼠足肿胀的治疗作用,对踝关节局部组织病理形态损伤的治疗作用,用免疫组化方法检测滑膜组织中VEGF的表达水平,利用基因芯片技术测定外周血淋巴细胞、肝组织中的VEGF的基因表达情况。结果益肾蠲痹丸高、中、低剂量组大鼠踝关节肿胀程度明显减轻,与模型组比较差异显著(P<0.05、0.01、0.001)。益肾蠲痹丸高、中、低剂量组与模型组比较,滑膜细胞增生减轻,滑膜组织充血水肿明显减轻,血管增生和浸润炎细胞数量减少,血管翳形成显著减少,纤维组织形成减少,软骨与骨组织破坏程度减轻。益肾蠲痹丸高、中剂量组与模型组比较滑膜组织中VEGF表达明显降低(P<0.05、0.01),低剂量组滑膜组织中VEGF表达亦有下降趋势。益肾蠲痹丸高、中剂量组能显著下调肝组织中VEGF-B基因的表达(fold change>1.5)。结论益肾蠲痹丸对CIA大鼠有显著治疗作用,能明显减轻大鼠踝关节肿胀程度,显著抑制CIA大鼠组织病理改变,能显著下调滑膜组织中VEGF的表达和肝组织中VEGF-B基因的表达,从而减少肝组织、滑膜组织中VEGF的量,抑制滑膜组织中血管翳的形成,减少对关节软骨和骨组织的破坏。 Objective To observe the therapeutic effect of Yishen Tiaopiai Pill on type II collagen-induced arthritis (CIA) rats and its effect on the pathological changes of the ankle joint. To investigate the effects of Yishen Tiabi Pill on rheumatoid arthritis (RA) and Correlation of vascular endothelial growth factor (VEGF). Methods The CIA rat model was established to observe the therapeutic effect of Yishen Tiaopiai Pill on foot swelling in CIA rats and the therapeutic effect on local histopathological injury of ankle joint. The expression of VEGF in synovial tissue was detected by immunohistochemistry , Using gene chip technology to determine the gene expression of VEGF in peripheral blood lymphocytes and liver tissue. Results Yishen Tiaopian high, medium and low dose groups of rat ankle joint swelling was significantly reduced, compared with the model group significant difference (P <0.05,0.01,0.001). Compared with the model group, the rats of Yishen Bibi Pill group showed less hyperplasia of synovial cells, less congestive and edema of synovial membrane, fewer vascular proliferating and infiltrating inflammatory cells, a significant decrease of angiogenesis and a decrease of fibrous tissue formation , Cartilage and bone tissue damage reduced. The expression of VEGF in synovial tissue of YSJB group was significantly lower than that of model group (P <0.05, 0.01), and the expression of VEGF in synovial tissue of low dose group also decreased. Yishen Bi Bi Wan high and medium dose groups could significantly down-regulate the expression of VEGF-B gene in liver tissue (fold change> 1.5). Conclusion Yishen Tiaopi Pill has a significant therapeutic effect on CIA rats, can significantly reduce the degree of ankle swelling in rats, significantly inhibit the pathological changes in CIA rats, can significantly down regulate the expression of VEGF in synovial tissue and VEGF- B gene expression, thereby reducing the amount of VEGF in liver and synovial tissue, inhibiting the formation of pannus in the synovium and reducing the destruction of articular cartilage and bone tissue.
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