青蒿琥酯诱导佐剂性关节炎滑膜细胞凋亡实验研究.pdfVIP

内 容 摘 要 目的探讨青蒿琥酯对佐剂性关节炎滑膜细胞凋亡的影响，证明其缓解佐剂性关 节炎病情的药理作用。方法 50 只雄性Wistar 大鼠随机分为6 组，空白组、模型组 （对照组）、青蒿琥酯I 组（高剂量组）、青蒿琥酯Ⅱ组（低剂量组）、青蒿琥酯加甲 氨喋呤组及甲氨喋呤组。除空白组外，余5 组用完全弗氏佐剂制备成佐剂性关节炎模 型。记录用药干预后各组关节肿胀指数、关节滑膜组织形态学特征，电镜下观察滑膜 细胞凋亡的早期形态学特征、流式细胞仪检测细胞凋亡率、免疫组化法检测滑膜组织 中凋亡相关因子Fas/FasL，Bcl-2，Bax，p53 以及核转录因子NF- κB 的表达情况。 结果 各实验组关节肿胀指数明显降低，用药前后自身对比及用药后与对照组比较差 异均有统计学意义（p0.01），滑膜的组织形态学特征得到了明显改善。电镜下可发 现滑膜细胞凋亡的早期形态学特征，流式细胞仪检测的滑膜细胞凋亡率各实验组均明 显高于对照组，差异有统计学意义（p0.01），免疫组化检测滑膜组织中 Fas、FasL 及Bax 被上调，Bcl-2 及NF- κB 被下调，与对照组比较差异有统计学意义（p0.05）。 结论 青蒿琥酯有诱导佐剂性关节炎病情缓解的作用，诱导滑膜细胞凋亡可能是其机 制之一。 关键词：青蒿琥酯 关节炎 细胞凋亡 Fas/FasL Bcl-2/Bax NF- κB II Abstract Objective: To observe the pharmacology effect of artesunate on inducing the alleviation of adjuvant arthritis(AA),and discuss the possibility of inducing apoptosis in synoviocyte of adjuvant arthritis(AA) with artesunate.Methods: fifty wistar rats were randomly divided into six groups:normal control, model control 、artesunate I group (high doses) 、 artesunate II group (low doses) 、artesunate plus MTX group, MTX group. Apart from normal control,six groups were modeled to adjuvant arthritis with complete Freunds. After treating with artesunate or artesunate plus MTX, the arthrosis index(AI) and morphological character in synovial membrane tissue of every group rats were recorded. The early morphological character on apoptosis in synoviocyte was observed by electron microscopy, the apoptosis percentage of the synoviocyte were examined by flow cytometry(FCM). Fas/FasL ，Bcl-2 ，Bax, P53 that correlation with apoptosis and NF-κB expression in arthrosis synovial membrane tissue were examined by immunohisto chemistry(IHC).Res