复元胶囊对兔骨关节炎关节软骨uPAuPARPAI.doc

复元胶囊对兔骨关节炎关节软骨uPA、uPAR、PAI及NF-κB表达的影响 张文亮1,2，李荣亨1，王淑美3，牟方政1，贾 平1 （400016重庆，重庆医科大学附属第一医院中西医结合科1； 400030重庆，重庆电力医院中医科2；重庆401331，重庆医科大学中医药学院临床教研室3） [摘要] 目的 观察复元胶囊(Fuyuan capsule，Fyc)对实验性兔膝骨关节炎（osteoarthritis，OA）软骨中尿激酶型纤溶酶原激活物(urokinase-type plasminogen activator，uPA)、uPA受体(uPA receptor，uPAR)、血浆酶原激活酶抑制因子(plasminogen activator inhibitor，PAI)的影响,探讨其对实验性兔膝OA的作用机制。方法：48只采用膝关节石膏制动法结合d-半乳糖皮下注射6周建立兔衰老骨关节炎模型，实验随机分为正常组、模型组、盐酸氨基葡萄糖胶囊90 mg/（kg·d）组，复元胶囊低、中、高剂量组[1350、2700、5400 mg/（kg·d）]共6组，每组8只，造模当日开始灌胃，1次/d，连续10 周。HE染色关节软骨Mankin’s评分，免疫组织化学法检测各组软骨组织中uPA、uPAR、PAI的表达，Western blot检测各组软骨组织中uPA、NF-κB的表达。结果：复元胶囊高剂量组和盐酸氨基葡萄糖组治疗后，兔OA关节软骨Mankin’s评分明显降低，免疫组化检测显示uPA及uPAR表达明显降低而PAI表达明显升高，Western blot检测显示NF-κB及uPA的表达受到明显抑制，与模型组比较差异有统计学意义（P0.01），复元胶囊高剂量组对NF-κB的抑制作用强于盐酸氨基葡萄糖组（P0.05），对其余指标的影响与盐酸氨基葡萄糖组比较差异无统计学意义（P0.05）。结论：复元胶囊能显著降低兔关节软骨中uPA、uPAR、NF-κB的表达，明显升高PAI的表达，提示复元胶囊可能通过调控uPA系统和NF-κB信号通路对骨关节炎发挥防治作用。 [关键词] 复元胶囊；兔膝骨关节炎；uPA；uPAR；PAI；NF-κB The effects of Fuyuan capsule on the expression of uPA，uPAR，PAI and NF-κB in knee osteoarthritis cartilage of rabbit ZHANG Wen-liang1,2， LI Rong-heng1，WANG Shu-mei3, MU Fang-zheng1, JIA Ping1 （1 Department of Traditional Chinese and Western Medicine，the First Affiliated Hospital， Chongqing Medical University，Chongqing 400016; 2 Department of Traditional Chinese Medicine，Chongqing Electric Power Hospital , Chongqing 400030；3 Department of Clinical Teaching and Researching, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 401331） [Abstract] Objective To investigate the effects of FuYuan capsule（Fyc）on expression of urokinase-type plasminogen activator (uPA)，uPA receptor (uPAR)，plasminogen activator inhibitor (PAI) and NF-κB in cartilage tissues of experimental osteoarthritis（OA）of rabbits. Methods 48 New Zealand rabbits osteoarthritis model was induced by combined injection of D-galactose and plaster immobilization . The experiment were divided into 6 groups randomly，8 rabbits in each group: normol group，model group，Glucosamine hyd