祛痹方对胶原诱导性关节炎大鼠氧自由基代谢及低氧诱导因子-1α水平的影响  

Effect of Qubi Recipe on Changes of Oxygen Free Radical Metabolism and Hypoxia-inducible Factor-1α in Collagen-induced Arthritis Rats

作　　者：赵宏艳[1] 杜中平[2] 李鸿泓[3] 肖诚[4] 王燕[5] 刘梅洁[1] 吕诚[6] 李艳[1] 刘红[1] 杨金生[7] 吕爱平[6] 鞠大宏[1] 

机构地区：[1]中国中医科学院中医基础理论研究所,北京100700 [2]北京市昌平区沙河医院心内科,北京102206 [3]北京市石景山区中医医院,北京100043 [4]中日友好医院临床医学研究所,北京100029 [5]民航总医院病理科,北京100123 [6]中国中医科学院中医临床基础医学研究所,北京100700 [7]中国中医科学院针灸研究所,北京100700

出　　处：《中国中西医结合杂志》2014年第9期1108-1112,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：重大新药创制科技重大专项(No.2009ZX09502-019)

摘　　要：目的观察祛痹方对Ⅱ型胶原诱导的免疫性关节炎模型大鼠氧自由基代谢物超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)及低氧诱导因子(hypoxia-inducible factor,HIF)-1α的影响,探讨祛痹方对类风湿关节炎(rheumatoid arthritis,RA)的治疗作用及其机制。方法选用SPF级雄性SD大鼠72只,随机选取1 2只作为空白对照组,其余60只采用尾根部皮下注射Ⅱ型胶原与不完全弗氏佐剂的方法 诱导制备关节炎模型,免疫15天后,将造模大鼠随机分为胶原诱导性关节炎(collagen-induced arthritis,CIA)模型组、雷公藤多苷治疗组、祛痹方高剂量及低剂量组,每组15只,予以灌胃给药,祛痹方高剂量组:6.66 g/(kg·d);祛痹方低剂量组:3.33 g/(kg·d);雷公藤多苷组:9.68 mg/(kg·d);空白对照组和CIA模型组大鼠灌服等体积纯净水。每日1次,连续4周。饲养期间测量大鼠踝关节肿胀度。治疗4周后处死动物,采用比色法测定血浆中SOD、MDA和GSH-P×活性;采用免疫组化法检测大鼠膝关节HIF-1α的表达。结果 (1)与CIA模型组比较,祛痹方高剂量组与雷公藤多苷组大鼠关节肿胀度均显著减轻(P<0.01,P<0.05),且祛痹方高剂量组关节肿胀度明显轻于雷公藤多苷组(P<0.05);(2)与CIA模型组比较,雷公藤多苷组及祛痹方高、低剂量组大鼠血浆GSH-P×活性明显升高,MDA活性降低,雷公藤多苷和祛痹方高剂量组大鼠血浆SOD活性明显升高(均P<0.05);(3)与CIA模型组比较,祛痹方高剂量组及雷公藤多苷组大鼠膝关节HIF-1α表达水平明显降低(P<0.05),祛痹方低剂量组有下降趋势,但差异无统计学意义(P>0.05)。结论祛痹方可显著减轻CIA模型大鼠踝关节肿胀程度,其疗效优于雷公藤多苷。其作用机制可能是通过下调关节HIF-1α表达及调节抗氧化水平,从而达到治疗CIA的作用。Objective To observe the effect of Qubi Recipe（QR） on the expression of superoxide dismutase（SOD）,malondialdehyde（MDA）,glutathione peroxidase（GSH-Px）,and hypoxia-inducible factor（HIF）-1α in rats with type Ⅱ collagen-Ⅰ induced arthritis（CIA）,and to explore its therapeutic roles and mechanism.Methods Totally 72 male SD rats of SPF grade were recruited.Twelve were randomly selected as the blank control group.The CIA model was established in the rest 60 rats by subcutaneously injecting type Ⅱ collagen of bovine emulsion from the tail root and induction of incomplete Freund＇s adjuvant.On day 15 after primary immunization rats were randomly divided into four groups,i.e.,the CIA model group,the Tripterygium Glycosides（TG） group（at the daily dose of 9.68 mg/kg body weight）,the high dose QR group（at the daily dose of 6.66 g/kg body weight）,and the low dose QR group（at the daily dose of 3.33 g/kg body weight）,15 in each group.Corresponding medication was given to rats in all groups by gastrogavage once daily for 4 successive weeks.An equal volume of pure water was given to rats in the blank control group and the CIA model group by gastrogavage,once daily for4 successive weeks.The swelling degree of the joints was measured.Rats were sacrificed after 4-week treatment.Plasma levels of SOD,MDA,and GSH-Px were measured with colorimetric method.The expression of HIF-1α was detected by immunohistochemistry.Results（1） Compared with the CIA model group,the swelling degree of the joints was significantly alleviated in the TG group and the high dose QR group（P〈0.01,P〈0.05）,and it was obviously milder in the high dose QR group than in the TG group（P〈0.05）.（2） Compared with the CIA model group,the activities of GSH-Px could be obviously elevated and activities of MDA lowered in the TG group,the high dose QR group,and the low dose QR group（P〈0.05）.Plasma activities of SOD could be obviously elevated in the high dose QR group and the TG group（P〈0.05）.（3

关 键 词：祛痹方 Ⅱ型胶原诱导的免疫性关节炎 超氧化物歧化酶 丙二醛 谷胱甘肽过氧化物酶 低氧诱导因子-1Α 

分 类 号：R285.5[医药卫生—中药学]