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[摘要]
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。
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[Abstract]
Objective To observe the therapeutical effect of Yishen Juanbi Pill (YJP) on type Ⅱ collagen induced arthritis (CIA) in rats and the histopathologic changes in ankle joint and to explore its possible mechanism on rheumatoid arthritis (RA). Methods The therapeutical effect of YJP on CIA rat paw swelling and the histopathologic morphology of the local tissue of ankle joint were observed by the type Ⅱ CIA rat model. The expression of VEGF of the synovial membrane was assayed by the immunohistochemical method. The changes in VEGF gene expression of peripheral lymphocytes and hepatic tissue were analyzed with gene chip after the treatment with YJP. Results The decreased swelling degrees of foot of rats in low-, mid-, and high-dose YJP groups were increased obviously than that of the model group (P<0.05, 0.01, and 0.001). As compared with the model group, YJP could produce the decreases in hyperplasia of synovial cells, congestion and dropsy of synovium, hyperplasia of blood vessel, infiltration of inflammatory cell, formation of pannus, fiber texture, and cartilage and bone damages. Expression of VEGF in synovial cells was clearly inhibited by YJP in the high- and mid-dose groups compared to the control group (P<0.05, 0.01). YJP in the high- and mid-dose groups significantly reduced the hyperactivity of VEGF-B gene expression in hepatic tissues (fold change > 1.5). Conclusion YJP can significantly inhibit joint swelling. YJP can significantly down-regulate the VEGF-B gene expression, thereby inhibit the formation of synovial tissue pannus and reduce cartilage and bone damages.
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