三氧化二砷治疗鸡卵蛋白诱导日本大耳白兔类风湿关节炎的初步观察

Therapeutic effect of ATO on rabbit rheumatoid arthritis induced by chicken ovalbumin

目的探讨三氧化二砷对鸡卵蛋白诱导日本大耳白兔致类风湿关节炎模型的滑膜组织核因子NF-κB(p65)表达活性及血清中白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)水平的影响。方法 48只日本大耳白兔随机分为模型组、正常对照组、三氧化二砷低剂量组(1.0 mg·kg-1·d-1)、三氧化二砷中剂量组(2.0 mg·kg-1·d-1)、三氧化二砷高剂量组(4.0 mg·kg-1·d-1)、醋酸泼尼松龙组(10 mg·d-1),每组8只。成功建立卵蛋白诱导关节炎模型后,分别给药2周;采用酶联免疫吸附法(ELISA)检测兔外周血中的IL-1、TNF-α,免疫组化实验方法检测核因子(NF-κB)(p65)在各组动物模型中的表达情况。结果卵蛋白诱导法可以成功诱导兔的关节炎,模型组外周血中的IL-1、TNF-α含量较正常对照组升高(P<0.05);三氧化二砷各剂量组兔的关节炎症状有不同程度改善,IL-1、TNF-α含量较模型组降低(P<0.05);免疫组化结果显示,模型组关节滑膜的NF-κB(p65)表达较正常组增强(P<0.05),而三氧化二砷各剂量组关节滑膜的NF-κB(p65)表达随砷剂剂量的增加表达减弱,但仍然强于正常对照组(P<0.05)。结论三氧化二砷对实验性类风湿关节炎日本大耳白兔模型有治疗作用。其机制可能与抑制了滑膜细胞中NF-κB(p65)活性和表达,降低了炎性因子IL-1、TNF-α的水平有关。

Objective To observe the difference of transcription factor NF-κB （p65 ）in the rabbit with rheumatoid arthritis（RA）mod-el induced by chicken ovalbumin as well as the level of IL-1 and TNF-αin the serum,and to explore the possible mechanism of treating RA with arsenic trioxide （ATO）.Methods Forty-eight Japanese big-ear rabbits （JBRs）were randomized into 6 groups after the mod-els had been injected with ovalbumin successfully,which included the control group （group A,n=8）,the model group （group B,n=8）,low-dose ATO group （group C,1.0 mg·kg-1·d-1,n=8）,medium-dose ATO group （group D,2.0 mg·kg-1·d-1,n=8）, high-dose ATO group （group E,4.0 mg·kg-1 ·d-1 ,n=8）and prednisolone acetate group （group F,10 mg·d-1 ,n=8）.Drugs were given for 2 weeks after the successful establishment of the rheumatoid arthritis model induced by chicken ovalbumin.ELISA and immunohistochemical experimental method were adopted to test the level of IL-1 and TNF-αin peripheral blood and the expressions of NF-κB（p65 ）in various groups.Results Chicken ovalbumin could induce the arthritis in rabbits.Compared with the control group, the levels of IL-1 and TNF-αin peripheral blood in the model group increased（P〈0.05）.Symptoms of arthritis in different ATO groups were decreased and their levels of IL-1 and TNF-αwere lower than those in the model group （P〈0.05）.Immunohistochemical findings showed that the expression of NF-κB（p65 ）in synovium of joint in the model group was greater than that in the control group （P〈0.05）.The expression of NF-κB（p65）in respective ATO groups decreased with the increased dose of ATO,yet still greater than that in the control group （P〈0.05）.Conclusions ATO has therapeutical effect on rheumatoid arthritis model of rabbits,the mecha-nism of which may be associated with the inhibition of NF-κB（p65 ）in synovium of joint and decreasing levels of IL-1 and TNF-α.