右归丸对膝骨性关节炎模型鼠基质金属蛋白酶及炎性因子表达的影响

Effect of Yougui pill on serum MMPs and inflammatory factors in rats with knee osteoarthritis

目的观察右归丸对膝骨性关节炎大鼠血清基质金属蛋白酶和炎症因子含量的影响,探讨右归丸对膝骨性关节炎是否具有治疗作用。方法 SPF级SD大鼠60只,随机分为假手术组、模型组、右归丸低、中、高剂量组和硫酸氨基葡萄糖组,每组10只。采用改良Hulth法复制膝骨关节炎大鼠模型。造模6周后,假手术组和模型组灌服蒸馏水,其他4组灌服相应的药物,干预8周后,HE染色法观察大鼠膝关节软骨的形态变化及Mankin评分,ELISA法检测大鼠血清中MMP-1、MMP-3、MMP-13、TIMP-1、IL-1β、IL-6和TNF-α的含量。结果与假手术组比较,模型组大鼠关节软骨Mankin评分显著升高,血清MMP-1、MMP-3、MMP-13、IL-1β、IL-6、TNF-α含量升高(均P<0.05);而其血清TIMP-1含量降低,差异有统计学意义(均P<0.05)。与模型组比较,右归丸高剂量组和硫酸氨基葡萄糖组Mankin评分降低,同时,右归丸高剂量组和硫酸氨基葡萄糖组大鼠血清MMP-1、MMP-3、MMP-13、L-1β、IL-6、TNF-α含量均下降(均P<0.05);而其TIMP-1升高,差异有统计学意义(P<0.05)。结论右归丸可能是通过抑制基质金属蛋白酶活性和炎症因子含量表达来延缓KOA软骨的退变。

Objective To observe the effect of Yougui pill on serum levels of matrix metalloproteinase（ MMPs） and inflammatory cytokines in rats with knee osteoarthritis（ KOA）. Methods Sixty SD rats were randomly divided into sham group,model group,Yougui pill low-dose,middle-dose,and high-dose group,and glucosamine sulfate group,with 10 rats in each group.KOA model was induced with modified Hulth method for 6 weeks. Animals in sham group and model group received equal volume of distilled water orally. Animals in the rests groups received according drugs. After 8 weeks,HE staining was adopted to observe the pathological changes of articular cartilage in each group. The chondrocyte morphology was observed and Mankin score was counted. ELISA was adopted to detect the serum levels of MMP-1,MMP-3,MMP-13,TIMP-1,IL-1β,IL-6,and TNF-α.Results Compared with the sham group,Mankin score increased significantly in model group（ P 〈 0. 05）. Meantime,the levels of MMP-1,MMP-3,MMP-13,IL-1β,IL-6,and TNF-α increased significantly,but TIMP-1 level decreased obviously in the model group（ P 〈 0. 05）. Compared with the model group,Mankin score decreased in Yougui pill high-dose group and glucosamine sulfate group. Meantime,the levels of MMP-1,MMP-3,MMP-13,IL-1β,IL-6,and TNF-α decreased,but TIMP-1 level increased in Yougui pill high-dose group and glucosamine sulfate group（ P 〈 0. 05）. Conclusion Yougui pill inhibits cartilage degeneration by down regulation of the levels of MMP and inflammatory factors in KOA.