胡蜂毒提取物对胶原诱导性类风湿性关节炎大鼠的作用研究

目的建立胶原诱导性类风湿关节炎(collagen-induced arthritis,CIA)大鼠模型来探讨胡蜂毒提取物对大鼠类风湿性关节炎(rheumatoid arthritis,RA)的治疗作用。方法将SD大鼠随机分为正常组、模型组、阳性对照组(注射用蜂毒冻干粉,1.25 mg·kg^-1)和胡蜂毒提取物低、中、高剂量(0.125、0.25、0.5 mg·kg^-1)组,除正常组外,其余各组采用多点注射鸡Ⅱ型胶原加完全弗氏佐剂的方法来诱导大鼠RA模型,每7 d一次,共14 d。造模结束后,各给药组于足趾皮下注射对应剂量的药物,连续给药14 d。分别于造模前、造模第14天和给药第14天测量大鼠踝关节直径和周长,并进行AI评分;观察大鼠脏器指数和踝关节组织HE染色的变化;采用酶联免疫吸附测定(ELISA)检测大鼠血清中相关炎症因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、IL-8、前列腺素(PG)E-2、环氧化酶(COX)-2和类风湿因子免疫球蛋白(Ig)G、Ig A、Ig M的含量变化;利用流式细胞术检测大鼠脾脏T细胞亚群的变化。结果与模型组比较,胡蜂毒提取物对CIΑ大鼠的关节肿胀(直径及周长)抑制效果显著(P<0.01),能明显降低其AI评分(P<0.01或P<0.05),能不同程度恢复大鼠的脏器指数(P<0.01或P<0.05),改善踝关节组织病理学结构病变,降低大鼠血清中各炎症因子和类风湿因子的表达(P<0.01或P<0.05),调节和改善T细胞亚群比例的紊乱(P<0.01或P<0.05)。结论胡蜂毒提取物对CIA大鼠具有较好的治疗作用,这与其对炎症细胞因子网络的调控和对免疫的调节有关系。

Effect of Wasp Venom Extract on Collagen-induced Arthritis in Rats

OBJECTIVE The rat model of collagen-induced arthritis(CIA)was successfully established to investigate the therapeutic effect of wasp venom extract on rheumatoid arthritis(RA)rats.METHODS The rats were randomly divided into normal group,model group,positive control group(bee venom lyophilized powder for injection,1.25 mg·kg^-1)and low,medium and high dose(0.125,0.25,0.5 mg·kg^-1)of wasp venom extract groups,in addition the normal group,the other group rats were induced by chicken type Ⅱ collagen and complete Freund’s adjuvant which was multi-point injected into the left hindfoot of rats,once every 7 d for 14 d.After successful modeling,the rats were given corresponding dose of drugs continuous administration for 14 d.The diameter and perimeter of the ankle joint and AI score of the rats were measured before modeling,on the 14 th day of modeling and on the 14 th of administration,respectively;The changes of organ index and HE staining in ankle tissue were observed.The contents of inflammatory factor(IL-1β,IL-6,TNF-α,IL-8,PGE-2,COX-2)and rheumatoid factors(Ig G,Ig A,Ig M)in serum of rats were detected by ELISA.The changes of T lymphocyte subsets in spleen tissue of rats were detected by flow cytometry.RESULTS Compared with the model group,the extract of wasp venom had significant inhibitory effect on joint swelling(diameter and perimeter)of CIA rats(P<0.01),The joint index scores of CIA rats was decreased(P<0.01 or P<0.05).The organs index of rats restored to varying degrees(P<0.01 or P<0.05),to improved pathological structure of ankle joint,and decreased the expression of inflammatory and rheumatoid factors in serum of rats(P<0.01 or P<0.05),to regulate and improve the proportion of T lymphocyte subsets(P<0.01 or P<0.05).CONCLUSION The extract of wasp venom has significant therapeutic effect on CIA rats,which is related to its regulation of inflammatory cytokine network and immunity.