禹州漏芦总黄酮对类风湿关节炎大鼠治疗机制研究

Treatment of rheumatoid arthritis with flavonoids of Echinps latifolius Tausch in rat model

目的：研究禹州漏芦总黄酮（FELT）对类风湿关节炎大鼠模型的治疗作用及病理机制的影响。方法：50只SD雄性大鼠随机分为正常对照组、空白对照组和FELT 50 mg／kg组、100 mg／kg组、150 mg／kg组，每组10只。空白对照组采用完全弗氏佐剂于每只大鼠右后足趾皮内注射0．1 mL致炎的方法制备，正常对照组大鼠右后足趾皮内注射0．1 mL磷酸盐缓冲液。采用大鼠关节炎评分法和足爪肿胀评分法评价FELT对类风湿关节炎大鼠的治疗作用，采用实时定量PCR分别检测FELT灌胃治疗对类风湿关节炎大鼠滑膜组织中纤维连接蛋白和基质金属蛋白酶3 mRNA表达的影响，对类风湿关节炎大鼠成纤维样滑膜细胞（ FLS ）中促凋亡基因Bcl－2相关X蛋白（ Bax ）和半胱氨酸天冬氨酸蛋白酶3（ caspase 3）、抗凋亡基因Bcl－2表达的影响。结果：类风湿关节炎大鼠经FELT 50、100、150 mg／kg 3个剂量灌胃治疗后，其关节炎评分和足爪肿胀评分较空白对照组均显著减少（均P＜0．05）。空白对照组和FELT 50、100、150 mg／kg 3个剂量组关节滑膜组织中纤维连接蛋白平均相对表达量分别为2．53和1．80、1．76、1．67（均P＜0．05）；基质金属蛋白酶3平均相对表达量分别为2．67和1．69、1．46、1．45（均P＜0．05）；FLS中Bax平均相对表达量分别为0．30和0．56、0．58、0．60（均P＜0．05） ，caspase 3平均相对表达量分别为0．29和0．54、0．56、0．59（均P＜0．05） ，Bcl－2平均相对表达量分别为4．04和2．20、2．08、2．08（均P＜0．05）。结论：FELT可以改善类风湿关节炎大鼠关节炎的严重程度，其机制可能与促进FLS凋亡、抑制滑膜组织异常增殖有关。

Objective：To investigate the effect of Flavonoids extracted from Echinps latifolius Tausch（FELT） on rheumatoid arthritis （RA） in rat model.Method：Fifty SD rats were randomly divided into model group , control group , and low, medium, and high-dose FELT groups （n=10 in each group）.Complete Freund’s adjuvant （0.1 mL） was used to induce RA in rats .FELT in doses of 50 mg/kg, 100 mg/kg, 150 mg/kg was given to rats in low , medium and high-dose FELT groups by gavage , and same volume of PBS was given to rats in control group .The arthritis score and the paw swelling score were measured to evaluate the therapeutic effect of FELT .Real time qPCR was used to detect the mRNA expression of fibronectin and MMP 3 in synovial tissue and the mRNA expression of caspase 3, Bcl-2 and Bcl-2 associated X protein （ Bax） in fibroblast-like synoviocytes （ FLS） .Results：The arthritis score and the paw swelling score were significantly decreased in three FELT groups compared to RA model rats （ P〈0.05 ） .The relative expression levels of FN and MMP 3 mRNA in synovium of three FELT-treatment groups were significantly lower than those in model group （1.80, 1.76 and 1.67 vs 2.53;1.69 , 1.46 and 1.45 vs 2.67 , respectively , all P〈0.05 ） . The relative expression levels of Bax and caspase 3 mRNA in FLSs of three FELT groups were higher than those in model group （ 0.56 , 0.58 and 0.60 vs 0.30;0.54 , 0.56 and 0.59 vs 0.29 , respectively , all P〈0.05 ）; while the relative expression levels of Bcl-2 mRNA in FELT groups were lower than that in model group （ 2.20 , 2.08 and 2.08 vs 4.04 , respectively , P〈0.05 ） .Conclusion：FELT may inhibit the synovium proliferation in RA model rats through promoting the FLS apoptosis .