风湿宁胶囊对RA兔关节滑膜组织MMP-3、MMP-9表达的影响  

Effect of fengshining capsules on the expressions of MMP-3 and MMP-9 in joint synovial tissue of the rabbits with rheumatoid arthritis

作　　者：马小娟 冯振宇[1] 孟霜[1] 赵建平[1] 王虹娟[1] 陈佳丽 MA Xiao-juan;FENG Zhen-yu;MENG Shuang;ZHAO Jian-ping;WANG Hong-juan;CHEN Jia-li(Integrated Chinese and Western Medicine Hospital,Shanxi University of Traditional Chinese Medicine,Taiyuan Shanxi 030013)

机构地区：[1]山西中医学院中西医结合医院

出　　处：《世界中西医结合杂志》2019年第7期941-945,982,共6页World Journal of Integrated Traditional and Western Medicine

基　　金：国家自然基金面上项目(81273981)

摘　　要：目的观察风湿宁胶囊对类风湿关节炎滑膜组织基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-9(MMP-9)表达的影响,探讨风湿宁胶囊治疗类风湿关节炎的机制。方法将120只雄性新西兰白兔随机分为正常组、模型组、风湿宁低剂量组、风湿宁中剂量组、风湿宁高剂量组、甲氨蝶呤组,每组20只。除正常组外,其余各组建立类风湿关节炎风寒湿痹病证结合模型,造模成功以后,风湿宁低、中、高剂量组分别给予0.33 g/kg、0.66 g/kg、1.32 g/kg的风湿宁胶囊水溶液,甲氨蝶呤组给予1.0 mg/kg的甲氨蝶呤片水溶液,正常对照组灌胃生理盐水,各组按4 ml/kg体重灌胃,1次/d,连续7 d。应用免疫组织化学法(IHC)和实时荧光定量聚合酶链式反应(Real-time PCR)法检测各组兔关节滑膜组织MMP-3、MMP-9蛋白和mRNA的相对表达量。结果与正常组比较,模型组MMP-3、MMP-9蛋白与mRNA表达明显增高,有显著性差异(P<0.05,P<0.01);与模型组比较,风湿宁高剂量与风湿宁中剂量给药后可明显降低RA兔滑膜组织MMP-3、MMP-9蛋白与mRNA的表达(P<0.05,P<0.01),作用与阳性对照药物甲氨蝶呤无明显差异(P>0.05)。结论风湿宁胶囊能够降低关节滑膜组织中与关节软骨基质降解和滑膜血管翳的生成相关的重要蛋白酶MMP-3、MMP-9蛋白与mRNA的表达,这可能是其治疗类风湿关节炎的重要机制。Objective To observe the effect of fengshining capsules on the expressions of matrix metalloproteinases-3(MMP-3)and matrix metalloproteinases-9(MMP-9)in joint synovial tissue of the rabbits with rheumatoid arthritis(RA)and explore the mechanism of fengshining capsules in treatment of RA.Methods A total of 120 male New Zealand white rabbits were randomized into a normal group,a model group,a fengshineng low-dose group,a fengshineng middle-dose group and a fengshineng high-dose group,and methotrexate group,20 rabbits in each one.Except the normal group,The model of RA and bi syndrome of wind,cold and damp was prepared in the rest groups.After successful modeling,the solution of fengshining capsules,0.33 g/kg,0.66 g/kg and 1.32 g/kg was given in the low-dose group,the middle-dose group and the high-dose group of fengshining successively.In the methorexate group,the solution of methorexate tablets,1.0 mg/kg was given.In the normal control group,physical saline was used.The intragastrical administration was at 4 ml/kg of body weight in each group,once a day,consecutively for 7 days.The immunolhistochemistry and real-time PCR methods were adopted to determine the protein and mRNA expressions of MMP-3 and MMP-9 in the joint synovial tissue of rabbits in each group.Results Compared with the normal group,the protein and mRNA expressions of MMP-3 and MMP-9 were increased in the model group,indicating the significant difference(P<0.05,P<0.01).Compared with the model group,the protein and mRNA expressions of MMP-3 and MMP-9 were reduced obviously after medication in the high-dose and middle-dose fengshining group(P<0.05,P<0.01),which was not different significantly as compared with the positive reference drug,methorexate(P>0.05).Conclusion Fengshining capsules reduce the protein and mRNA expressions of MMP-3 and MMP-9,the important proteases related to degradation of articular cartilage matrix and the formation of synovial vessel,which may be the important mechanism for the treatment of RA.

关 键 词：风湿宁胶囊 类风湿关节炎 风寒湿痹证 基质金属蛋白酶-3 基质金属蛋白酶-9 

分 类 号：R285.5[医药卫生—中药学]