风湿骨病候选复方祛风四味方对大鼠佐剂性关节炎治疗作用及机制研究

Therapeutic Effect and Mechanism of Candidate Formula Qufeng Siwei Fang for Treating Rheumatoid Bone Diseases on Adjuvant Arthritis Rats

目的观察腰痛宁(YTN)有效部位减毒拆方祛风四味方(QFSWF)对佐剂性关节炎(AA)继发性病变、相关炎症因子以及机体免疫功能的影响,探究QFSWF对类风湿性关节炎的可能作用机制及其作为风湿骨病候选中药复方的可行性。方法随机将SD大鼠分为正常对照组,模型组,雷公藤多苷组(LGT,40 mg·kg^(-1)),YTN组(150 mg·kg^(-1)),QFSWF低、中、高剂量组(20,40,80 mg·kg^(-1)),于大鼠左后足跖皮下注射弗氏完全佐剂(CFA,10 mg·m L^(-1))0.1 m L进行模型复制,观察各组大鼠足跖肿胀度及关节炎指数(AI);通过酶联免疫吸附法(ELISA)检测AA大鼠血清中的细胞因子白细胞介素1β(IL-1β)、肿瘤坏死因子(TNF-α)、前列腺素E_2(PGE_2)的水平;摘取大鼠脾脏、胸腺,观察药物对AA大鼠免疫器官的影响。结果与模型组比较,QFSWF组的大鼠脾脏指数及胸腺指数显著降低(P<0.05,P<0.01),体质量显著增加(P<0.05,P<0.01),QFSWF组、YTN组和LGT组的大鼠继发性病变显著受抑制,大鼠血清中的炎症因子IL-1β,TNF-α以及PGE2水平显著降低(P<0.05,P<0.01),且QFSWF组抑制IL-1β,TNF-α释放水平的活性显著优于YTN组(P<0.01)。结论QFSWF通过降低炎症因子水平,提高机体的免疫能力而对佐剂型关节炎产生疗效,总体治疗指标优于YTN,可作为治疗风湿骨病候选中药复方。

Objective To study the effect of Qufeng Siwei Fang（QFSWF）, a dissembled formula developed from Yaotongning（YTN） capsule, on secondary lesions of adjuvant arthritis（AA）, correlative inflammatory factors and immune function of AA in rats,and to probe the possible therapeutic mechanism of the formula and the feasibility of the formula being used as a candidate formula for treating rheumatoid bone diseases. Methods AA was induced by injection of complete Freund＇s adjuvant（CFA,10 mg·mL^-1） 0.1 mL into the left hind metatarsal footpad of rats. Rats were distributed into normal group,model group,tripterysium glycosides（TG）group（40 mg·kg^-1）,YTN group（150mg·kg^-1）, and high-, middle- and low- dose QFSWF groups（80, 40, 20 mg·kg^-1）. After the AA model was established successfully,the paw edema and arthritis index（AI） of AA rats were observed and recorded. The levels of interleukin 1β（IL- 1β）,tumor necrosis factor alpha（TNF- α）and prostaglandin E2（PGE2）in the serum of AA rats were detected by enzyme- linked immunosorbent assay（ELISA）. The spleen and thymus were removed and weighed for detecting the drug influence on the immune organs. Results Compared with the model group, the spleen index and thymus index were reduced significantly（P〈0.05,P〈0.01）,and the rat body weight was significantly increased in QFSWF groups（P〈0.05,P〈0.01）. The serum levels of IL- 1β,TNF- α and PGE2 in QFSWF groups,YTN group and TG group were significantly decreased（P〈0.05, P〈0.01）, and the secondary affection of the AA rats was significantly inhibited. Moreover, the activities of QFSWF in inhibiting the release of IL- 1β and TNF- α were significantly superior to those of YTN（P〈0.01）. Conclusion QFSWF has certain therapeutic effect on AA by reducing serum inflammatory factors and improving the body immunity,and its effect is better than YTN. QFSWF can be a preferred candidate of Chinese medicine formula for treatment of rheumatoid bone disease.