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  

Fuyuan capsule downregulates uPA,uPAR and NF-κB while upregulates PAI in knee cartilage of osteoarthritis rabbits

作　　者：张文亮[1,2] 李荣亨[1] 王淑美[3] 牟方政[1] 贾萍[1] 

机构地区：[1]重庆医科大学附属第一医院中西医结合科,重庆400016 [2]重庆电力医院中医科,重庆400030 [3]重庆医科大学中医药学院临床教研室,重庆401331

出　　处：《第三军医大学学报》2011年第20期2172-2176,共5页Journal of Third Military Medical University

基　　金：重庆市卫生局科研项目(2008-2-35)~~

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(plas-minogen activator inhibitor,PAI)的影响,探讨其对实验性兔膝OA的作用机制。方法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。48只新西兰兔根据体质量按随机区组法分为健康组、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[1 350、2 700、5 400 mg/(kg.d)],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胶囊组的兔OA关节软骨Mankin’s评分较模型组明显降低(P<0.01);免疫组化检测结果显示,复元胶囊高剂量组和盐酸氨基葡萄糖胶囊组uPA及uPAR表达明显降低,而PAI表达明显升高(P<0.01);Western blot检测结果显示,盐酸氨基葡萄糖胶囊组和复元胶囊高剂量组uPA及NF-κB均较模型组显著降低(P<0.01)。复元胶囊高剂量组对uPA的抑制作用与盐酸氨基酸葡萄糖胶囊组比较差异无统计学意义(P>0.05),但对NF-κB的抑制作用强于盐酸氨基酸葡萄糖胶囊组(P<0.05)。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。Objective To determine the efficiency of Fuyuan capsule（Fyc,a capsule containing several Chinese herbs） on the expression of urokinase-type plasminogen activator（uPA）,uPA receptor（uPAR）,plasminogen activator inhibitor（PAI） and NF-κB in the cartilage tissues of experimental osteoarthritis（OA） rabbits.Methods A total of 48 New Zealand rabbits were divided into 6 groups randomly with 8 rabbits in each group： normal group,model group,glucosamine hydrochloride capsule group [90 mg/（kg·d）] and low-,middle-and high-dose Fyc capsule groups [1 350,2 700 and 5 400 mg/（kg·d）].The rabbits of model and treatment groups were inflicted by combined injection of D-galactose and plaster immobilization into their left knee joint to produce osteoarthritis model.All drugs were given from the same day of modeling,by gavage injection,daily,for 10 weeks.Mankin＇s score was detected by light microscopy and HE staining.Then cartilage sections were analyzed by immunohistochemistry for uPA,uPAR and PAI.The protein expressions of uPA and NF-κB were detected by Western blotting.Results After treatment with high-dose Fyc and glucosamine hydrochloride capsule,the Mankin＇s score was decreased significantly when compared with model group（3.28±0.46 and 3.46±0.78 vs 8.73±0.94,P0.01）.Immunohistochemical staining indicated that the expression intensities and positive cell ratio of uPA and uPAR were decreased and those of PAI were increased,and Western blotting showed that the protein expressions of uPA and NF-κB were reduced significantly in high-dose Fyc and glucosamine hydrochloride capsule groups.Compared to the model group,all these difference were significantly（P0.01）.But there was no significant difference in the inhibiting effect to uPA in the high-dose Fyc and glucosamine hydrochloride groups（P0.05）,but the former group showed stronger effect on NF-κB reduction（P0.05）.Conclusion Fyc capsule downregulates uPA,uPAR and NF-κB,while upregulate PAI in the cartilage tissues of experimental

关 键 词：复元胶囊 骨关节炎 尿纤溶酶原激活物 纤溶酶原灭活剂 NF-ΚB 兔 

分 类 号：R285.5[医药卫生—中药学] R392.5[医药卫生—中医学]