北京医科大学学报
北京醫科大學學報
북경의과대학학보
JOURNAL OF BEIJING MEDICAL UNIVERSITY
2000年
3期
214-218
,共5页
李卫东%冉国侠%沈建英%滕惠玲%林志彬
李衛東%冉國俠%瀋建英%滕惠玲%林誌彬
리위동%염국협%침건영%등혜령%림지빈
关节炎,佐剂性%免疫耐受%胶原%鸡源性Ⅱ型胶原%白细胞介素-1
關節炎,佐劑性%免疫耐受%膠原%鷄源性Ⅱ型膠原%白細胞介素-1
관절염,좌제성%면역내수%효원%계원성Ⅱ형효원%백세포개소-1
Arthritis,adjuvant%Immune tolerance%Collagen%Chicken type Ⅱ collagen%IL-1
目的:评价口服鸡源性Ⅱ型胶原蛋白(chicken type Ⅱ collagen, CCⅡ)对胶原性关节炎(collagen-induced arthritis, CIA)小鼠的抗炎及免疫作用的影响.方法:以CCⅡ蛋白与福氏完全佐剂免疫昆明种小鼠,并于第21天强化免疫1次.CCⅡ于致敏前第5天即开始灌胃给药,共20 d.每周两次评价多发性关节炎评分.以ELISA法测定CIA小鼠血清抗CⅡ抗体.以流式细胞测定法测定小鼠脾T淋巴细胞亚型.以ELISA法测定佐剂性关节炎大鼠腹腔巨噬细胞IL-1分泌水平.结果:口服CCⅡ 5 μg.kg-1和50μg.kg-1可明显降低多发性关节炎评分值,而250 μg.kg-1剂量组则无作用;CCⅡ 5μg.kg-1剂量组可抑制CIA小鼠升高了的血清抗CⅡ抗体水平;口服CCⅡ可使CIA小鼠升高的L3T4+/Lyt-2+值有所降低.口服CCⅡ可使佐剂性关节炎大鼠升高了的IL-1水平有所降低.结论:口服CCⅡ可抑制CIA小鼠多发性关节炎的发生,此作用可能有体液免疫和细胞免疫两种机制参与.以上作用的发生为剂量依赖性的,即小剂量作用最强.
目的:評價口服鷄源性Ⅱ型膠原蛋白(chicken type Ⅱ collagen, CCⅡ)對膠原性關節炎(collagen-induced arthritis, CIA)小鼠的抗炎及免疫作用的影響.方法:以CCⅡ蛋白與福氏完全佐劑免疫昆明種小鼠,併于第21天彊化免疫1次.CCⅡ于緻敏前第5天即開始灌胃給藥,共20 d.每週兩次評價多髮性關節炎評分.以ELISA法測定CIA小鼠血清抗CⅡ抗體.以流式細胞測定法測定小鼠脾T淋巴細胞亞型.以ELISA法測定佐劑性關節炎大鼠腹腔巨噬細胞IL-1分泌水平.結果:口服CCⅡ 5 μg.kg-1和50μg.kg-1可明顯降低多髮性關節炎評分值,而250 μg.kg-1劑量組則無作用;CCⅡ 5μg.kg-1劑量組可抑製CIA小鼠升高瞭的血清抗CⅡ抗體水平;口服CCⅡ可使CIA小鼠升高的L3T4+/Lyt-2+值有所降低.口服CCⅡ可使佐劑性關節炎大鼠升高瞭的IL-1水平有所降低.結論:口服CCⅡ可抑製CIA小鼠多髮性關節炎的髮生,此作用可能有體液免疫和細胞免疫兩種機製參與.以上作用的髮生為劑量依賴性的,即小劑量作用最彊.
목적:평개구복계원성Ⅱ형효원단백(chicken type Ⅱ collagen, CCⅡ)대효원성관절염(collagen-induced arthritis, CIA)소서적항염급면역작용적영향.방법:이CCⅡ단백여복씨완전좌제면역곤명충소서,병우제21천강화면역1차.CCⅡ우치민전제5천즉개시관위급약,공20 d.매주량차평개다발성관절염평분.이ELISA법측정CIA소서혈청항CⅡ항체.이류식세포측정법측정소서비T림파세포아형.이ELISA법측정좌제성관절염대서복강거서세포IL-1분비수평.결과:구복CCⅡ 5 μg.kg-1화50μg.kg-1가명현강저다발성관절염평분치,이250 μg.kg-1제량조칙무작용;CCⅡ 5μg.kg-1제량조가억제CIA소서승고료적혈청항CⅡ항체수평;구복CCⅡ가사CIA소서승고적L3T4+/Lyt-2+치유소강저.구복CCⅡ가사좌제성관절염대서승고료적IL-1수평유소강저.결론:구복CCⅡ가억제CIA소서다발성관절염적발생,차작용가능유체액면역화세포면역량충궤제삼여.이상작용적발생위제량의뢰성적,즉소제량작용최강.
Objective: To assess the immunological effects by orally administering chicken type Ⅱ collagen(CCⅡ) on collagen-induced arthritis(CIA)mice. To assess the effect on producing IL-1 of peritoneal macrophage in adjuvant arthritis rats by orally administering CCⅡ. Methods: Arthritis were induced in Kunming mice by immunization with chicken type Ⅱ collagen with Freund's complete adjuvant, followed by an interperitoneal injection of CCⅡ 3 weeks later.Chicken type Ⅱ collagen was orally administered from 5 days prior to the induction of arthritis to 14 days after inducing arthritis model. The animals were examined visually twice weekly for polyarthritic signs of swollen and erythemic limbs. Quantitation of antibody level of CIA mice was measured by ELISA method. Subpopulations of T lymphocytes in mice were evaluated by flow cytometry method. IL-1 assay was evaluated by ELISA method. Results: Joint swelling was significantly reduced at a dose of 5 μg.kg-1 and 50 μg.kg-1 of CCⅡ, but not at 250 μg.kg-1. The level of anti-collagen antibodies was also reduced at a dose of 5 μg.kg-1 and 50μg.kg-1 (OD value from CIA model control 0.242±0.073 to CCⅡ 5 μg.kg-1 0.123±0.029 and CCⅡ 50 μg.kg-1 0.110±0.075 respectively). Subpopulations of T-lymphocytes were changed by orally administering of CCⅡ, and the ratio of L3T4+/Lyt-2+ was lowered (the ratio from 1.71 of CIA model control to 1.21, 1.51 of administered CⅡ 5 μg.kg-1, 50μg.kg-1 respectively.) after administering CCⅡ. IL-1 level can be reduced (the value from adjuvant arthritis model control 62.8±0.9 to 43.4±1.3, 49.7±0 ng.L-1 administered CⅡ 5 μg.kg-1, 50μg.kg-1 respectively). Conclusion: Arthritis sign in CIA animal model can be suppressed by oral CCⅡ. The effects may be involved by influencing the mechanisms both humoral and cellular immunity. The effects occurred at lower doses of CCⅡ. These results demonstrated the biologic relevance of by-stander suppression associated with oral tolerance, and the potential use of this approach to treat human inflammatory joint diseases.