Objective To establish an animal model of rheumatoid arthritis(RA),and to study the correlation between RA and intestinal permeability.Methods Forty rats were randomly divided into four groups: normal group(rats were given normal saline),group A(rats were gavaged with bovine type Ⅱ collagen,carbon tetrachloride(CCl4) and lipopolysaccharide(LPS) after pretreatment with 1 mg·kg-1 of aspirin for 2 weeks),group B(rats were gavaged with bovine type Ⅱ collagen,CCl4 and LPS after pretreatment with 5 mg·kg-1 of aspirin for 2 weeks),and group C(rats were gavaged with bovine type Ⅱ collagen,CCl4 and LPS after pretreatment with 10 mg·kg-1 of aspirin for 2 weeks),with 10 rats in each group.The arthritis index was scored and serum levels of immunoglobulin E(IgE),immunoglobulin G(IgG),interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were measured in all groups.The intestinal permeability was assessed by lactulose/mannitol test.In addition,pathological features of jejunum and fluorescence localization of bovine type Ⅱ collagen were observed.Results The morbidity rate in group C was significantly higher than that in group B(70.00% vs 30.00%,P<0.05).Compared with normal group,serum IgE,IgG,IL-6 and TNF-α levels significantly increased in groups B and C after intervention for 10 weeks(P<0.05 or P<0.01).The lactulose/mannitol test and immunofluorescence assay showed that the intestinal permeability increased and was positively correlated with the arthritis index(P<0.05).Conclusion High-dose aspirin administration caused a higher intestinal permeability than low-dose aspirin administration.Furthermore,RA was more prone to be induced after treatment with high-dose aspirin in rats.%目的 建立类风湿性关节炎(rheumatoid arthritis,RA)动物模型,探讨其与肠道通透性的相关性.方法将40只大鼠随机分为4组:生理盐水处理组(正常组)、1 mg·kg-1阿司匹林预处理大鼠2周后用牛Ⅱ型胶原蛋白+四氯化碳(CCl4)+脂多糖(LPS)灌胃组(A组)、5 mg·kg-1阿司匹林预处理大鼠2周后用牛Ⅱ型胶原蛋白+CCl4+LPS灌胃组(B组)、10 mg·kg-1阿司匹林预处理大鼠2周后用牛Ⅱ型胶原蛋白+CCl4+LPS灌胃组(C组),每组10只.对各组大鼠进行关节炎指数评分,分别检测大鼠血清中特异性抗体[免疫球蛋白E(IgE)和免疫球蛋白G(IgG)]和炎症细胞因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]的水平,通过双糖(乳果糖、甘露醇)实验检测大鼠肠道的通透性,观察大鼠空肠组织的病理表现及Ⅱ型胶原蛋白荧光定位.结果 C组大鼠致病率明显高于B组(70.00%比30.00%,P<0.05).与正常组比较,B、C 2组大鼠干预10周后血清中IgE、IgG水平,血清中IL-6、TNF-α水平均显著升高(P<0.05或P<0.01).双糖实验和肠组织免疫荧光实验显示,B、C 2组大鼠肠道通透性显著增加,且其与关节炎指数评分均呈正相关(均P<0.05).结论 高剂量阿司匹林处理后的大鼠肠道通透性比低剂量的高,且高剂量处理后的大鼠用牛Ⅱ型胶原蛋白更能诱发形成RA.
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