六味骨痹汤对兔骨关节炎滑膜组织的影响及与软骨修复的相关性研究  

Effects of Liuwei Gubi Decoction on Synovial Tissues in Rabbits with Osteoarthritis and Correlation with Cartilage Repair

作　　者：李媛[1] 彭力平[2] 余阗[2] 胡烈奎 赖锦泉 陈达 廖州伟 马笃军[2] LI Yuan;PENG Li-Ping;YU Tian;HU Lie-Kui;LAI Jin-Quan;CHEN Da;LIAO Zhou-Wei;MA Du-Jun(The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shrnzlien 518033 Guangdong,China;Section No. 1 of Orthopedics Dept., Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen518033 Ouangdong, China;Section No. 1 of Orthopedics Dept., Bao an Hospital of TraditionalChinese Me(li( ine( Group), Shenzhen 518101 Guangdong, China)

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518033 [2]深圳市中医院骨伤科一病区,广东深圳518033 [3]深圳宝安中医院(集团)骨伤科一区,广东深圳518101

出　　处：《广州中医药大学学报》2019年第5期702-707,共6页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金资助项目(编号:81804124);广东省中医药局科研项目(编号:20171245);深圳市医疗"三名工程"项目(编号:SZSM201812066)

摘　　要：【目的】通过观察六味骨痹汤对骨关节炎(OA)模型兔关节液中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、基质金属蛋白酶13(MMP-13)含量,滑膜、关节软骨形态及软骨Ⅱ型胶原蛋白表达的影响,探讨其对OA滑膜组织的修复作用及与关节软骨修复的相关性。【方法】将32只新西兰兔随机分为正常组、模型组、六味骨痹汤组和硫酸氨基葡萄糖组,每组8只。采用木瓜蛋白酶关节注射法建立兔OA模型。成功造模后,前2组每日给予10 mL生理盐水灌胃,后2组每日分别对应给予六味骨痹汤(剂量为3.8 g·kg-1·d-1)及硫酸氨基葡萄糖胶囊(剂量为77.0 mg·kg-1·d-1)灌胃。给药6周后,酶联免疫吸附分析(ELISA)检测各组实验兔关节液中TNF-α、IL-1β、MMP-13含量,按照Krenn标准及改良Mankin’s法分别对滑膜炎症程度及软骨损伤程度进行评分,并评价软骨标本中Ⅱ型胶原蛋白表达情况,最后分析关节滑膜炎症程度与软骨修复的相关性。【结果】六味骨痹汤组和硫酸氨基葡萄糖组关节液中TNF-α、IL-1β、MMP-13含量,滑膜炎症Krenn评分,关节软骨Mankin’s评分均较模型组显著降低(P<0.01),Ⅱ型胶原蛋白表达评分显著升高(P<0.05);2给药组组间比较,差异无统计学意义(P>0.05)。各组滑膜炎症的缓解与软骨的修复程度成较强的正相关性。【结论】六味骨痹汤对兔OA模型滑膜炎症有缓解作用,并且这种改变与Ⅱ型胶原蛋白高表达及OA软骨的修复程度相关。本研究明确了补肝肾、强筋骨类方药治疗OA滑膜炎的疗效及与软骨修复的相关性,也为中药治疗滑膜炎及软骨损伤性疾病提供数据支持及新的思路。Objective To observe the effects of Liuwei Gubi Decoction(LGD)on the contents of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and matrix metalloproteinase 13(MMP-13)in synovial fluid,the morphological feature of synovial membrane and articular cartilage,and the expression level of type II collagen protein in articular cartilage of osteoarthritis(OA)rabbit model,thus to explore its repair effect on osteoarthritic synovial tissues and the correlation with articular cartilage repair. Methods Thirty-two New Zealand rabbits were randomly divided into normal group,model group,LGD group and Glucosamine Sulfate Capsules(GSC)group,8 rabbits in each group. OA rabbit model was established by intra-articular injection of papain. After successful modeling, the first two groups were given 10 mL of normal saline daily, and the latter two groups were correspondingly given LGD(at the dosage of 3.8 g·kg^-1·d^-1)and GSC(at the dosage of 77.0 mg·kg^-1·d^-1),respectively. After medication for 6 weeks,the levels of TNF-α,IL-1β and MMP-13 in synovial fluid were detected by enzyme-linked immunosorbent assay(ELISA). The degrees of synovitis and cartilage injury were scored according to Krenn standard and modified Mankin’s method,and the expression of type II collagen protein in cartilage samples was evaluated. Finally,the correlation between the degrees of synovitis and cartilage repair was analyzed. Results The contents of TNF-α,IL-1β,MMP-13,Krenn score of synovitis and Mankin’s score of cartilage injury in LGD group and GSC group were significantly lower than those in the model group(P < 0.01),and the expression score for type II collagen protein was significantly increased(P < 0.05), there being no significant difference between LGD group and GSC group(P > 0.05). There was a strong positive correlation between the relief of synovitis and the degree of cartilage repair in various groups. Conclusion LGD can alleviate synovitis inflammation in rabbit OA model,and the mechanism is related with the increase of collag

关 键 词：六味骨痹汤 骨关节炎 滑膜炎 软骨修复 疾病模型 动物 兔 

分 类 号：K285.5[历史地理—历史学]