复方双氯芬酸钠对骨关节炎大鼠软骨形态及氧化应激的影响  

Effects of compound diclofenac sodium on cartilage morphology and oxidative stress in osteoarthritis rats

作　　者：周志洁 张兰云 李凤国 张国辉 Zhou Zhijie;Zhang Lanyun;Li Fengguo;Zhang Guohui(Department of Orthopedics and Sports Medicine,Hengshui People’s Hospital,Hengshui 053000,Hebei Province,China)

机构地区：[1]衡水市人民医院关节骨科运动医学科,河北省衡水市053000

出　　处：《中国组织工程研究》2023年第26期4154-4160,共7页Chinese Journal of Tissue Engineering Research

基　　金：河北省医科科学研究基金项目(20210551),项目负责人:张国辉;衡水市科技计划项目(1506),项目负责人:李凤国。

摘　　要：背景:复方双氯芬酸钠是镇痛解热、非类固醇药物,其被广泛用于缓解轻至中度疼痛,治疗类风湿关节炎、骨关节炎和强直性脊柱炎、骨关节炎、肌肉骨骼损伤等,但目前关于其对骨关节炎的作用机制报道较少。目的:探究复方双氯芬酸钠对骨关节炎大鼠基质金属蛋白酶1、软骨形态及氧化应激的影响。方法:采用木瓜蛋白酶关节腔内注射建立骨关节炎大鼠模型,将Wistar大鼠随机分为空白组,骨关节炎模型组、复方双氯芬酸钠低、中、高剂量组、塞来昔布组。测量各组大鼠右侧膝关节的肿胀程度;ELISA检测关节积液中肿瘤坏死因子α、白细胞介素1β、基质金属蛋白酶1水平,并检测氧化应激指标超氧化物歧化酶、丙二醛、谷胱甘肽过氧化物酶含量;比较各组大鼠关节软骨组织形态和Mankin评分;蛋白质印迹法检测关节软骨中基质金属蛋白酶1、基质金属蛋白酶3、基质金属蛋白酶13蛋白表达。结果与结论:①在造模后和给药前,和空白组相比,模型组大鼠右膝关节均出现了不同程度的红肿,但无紫红色斑和结节等变化;给药后,和模型组相比,复方双氯芬酸钠低、中、高剂量组和塞来昔布组大鼠右膝关节红肿程度明显减轻(P<0.05);②模型组大鼠关节腔积液中肿瘤坏死因子α、白细胞介素1β、基质金属蛋白酶1水平较空白组增加(P<0.05);低、中、高剂量组和塞来昔布组大鼠关节腔积液中肿瘤坏死因子α、白细胞介素1β、基质金属蛋白酶1水平均低于模型组(P<0.05);③和空白组相比,模型组大鼠超氧化物歧化酶活性和谷胱甘肽过氧化物酶含量均显著降低,丙二醛浓度升高(P<0.05);和模型组相比,各给药组大鼠超氧化物歧化酶活性和谷胱甘肽过氧化物酶含量均升高,丙二醛浓度均降低,且复方双氯芬酸钠高剂量组变化最显著(P<0.05);④模型组大鼠Mankin评分高于空白组(P<0.05);和模型组相比,各给BACKGROUND:Compound diclofenac sodium is an analgesic and antipyretic,non-steroidal drug,which has been widely used to relieve mild-to-moderate pain and treat rheumatoid arthritis,osteoarthritis and ankylosing spondylitis,and osteoarthritis,musculoskeletal injury.However,there are few reports on its mechanism of action on osteoarthritis.OBJECTIVE:To explore the effect of compound diclofenac sodium on matrix metalloproteinase 1,cartilage morphology and oxidative stress in osteoarthritis rats.METHODS:Rat models of osteoarthritis were established by intra-articular injection of papain and randomly divided into blank group,model group,low,middle-,and high-dose compound diclofenac sodium groups,and celecoxib group.The swelling degree of the right knee joint of rats was measured.ELISA was used to detect the contents of tumor necrosis factor-α,interleukin-1β,and matrix metalloproteinase 1 in the joint effusion.The levels of oxidative stress indicators,superoxide dismutase,malondialdehyde,glutathione peroxidase,were detected.Articular cartilage histology and Mankin score were compared between groups.Western blot was used to detect the protein expression of matrix metalloproteinases 1,3,and 13 in the articular cartilage.RESULTS AND CONCLUSION:After modeling and before administration,compared with the blank group,rats in the model group,low-,middle-,high-dose groups and celecoxib group all had different degrees of redness and swelling in the right knee joint,but no purple-red spots and nodules.After administration,the degree of redness and swelling of the right knee joint of rats in the model group was significantly reduced in the low-,middle-,high-dose groups and celecoxib group compared with the model group(P<0.05).The levels of tumor necrosis factor-α,interleukin-1β,and matrix metalloproteinase 1 in the joint effusion were significantly higher in the model group than the blank group(P<0.05),while these levels were significantly reduced after administration of low-,middle-,and high-dose compound diclofenac sodium and

关 键 词：复方双氯芬酸钠 骨关节炎 MMP-1 软骨形态 氧化应激 基质金属蛋白酶 

分 类 号：R446[医药卫生—诊断学] R318[医药卫生—临床医学] R496