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[摘要]
目的:研究森登-4对CIA大鼠CTLA-4/B7-1介导的免疫炎症的影响。方法:首先建立Wistar 大鼠CIA模型,分为6组,观察大鼠关节HE病理改变,采用酶联免疫吸附分析法检测大鼠血清中IL-6、TGF-β、sCTLA-4、B7-1的水平,利用免疫组化法检测踝关节CTLA-4、B7-1的IOD值,评估CTLA-4、B7-1的表达情况。结果:各治疗组踝关节HE 病理改变较模型组减轻。模型组IL-6 和sCTLA-4 水平较正常组显著升高(P<0.05);而模型组TGF-β和B7-1 (sCD80)水平较正常组却显著降低(P<0.05)。经过3疗程治疗,各药物治疗组比模型组IL-6 和sCTLA-4 水平降低(P<0.05),其中降低最明显的是森登-4高剂量组和甲氨蝶呤组,而各药物治疗组 TGF-β 和B7-1 (sCD80) 的水平较模型组则升高(P<0.05),森登-4高剂量组和甲氨喋呤组升高尤为显著。3疗程结束后,对比CTLA-4 IOD 值发现模型组较正常组显著降低(P<0.05);各治疗组CTLA-4 IOD 值相比于模型组则显著升高(P<0.05),表达显著升高的是甲氨蝶呤组和森登-4高剂量组。与正常组相比,模型组的CD80 IOD 值显著提升(P<0.05);与模型组相比,药物治疗组CD80 IOD 值显著降低(P<0.05),森登-4高剂量组和甲氨蝶呤组降低最明显。结论:森登-4可能通过介导CTLA-4/B7-1 相关免疫抑制反应缓解CIA 大鼠关节炎反应,且与森登-4的剂量相关。
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[Abstract]
Objective: To study the effect of Mongolian medicine senden-4 on CTLA-4 and B7-1(CD80) mediated immune inflammation in CIA rats. Methods: CIA rat model was established for arthritis index score and HE staining. Serum level of interleukin-6 (IL-6), TGF-β, sCTLA-4 and sCD80(B7-1) was detected with the method of enzyme-linked immunosorbent assay (ELISA). The IOD value of CTLA-4 and CD80 was detected with immunohistochemistry, and the expression level of CTLA-4 and CD80 in the ankle was determined, too. Results Compared with the model group, the pathological change of the drug treatment group were alleviated. Compared with the normal group, the levels of IL-6 and sctla-4 in the model group were significantly increased (P < 0.05), while the levels of TGF - β and B7-1 (sCD80) in the model group were significantly decreased (P < 0.05). Compared with the model group, the levels of IL-6 and sctla-4 in all drug treatment groups were decreased in varying degrees (P < 0.05), and the most obvious decrease was in senden-4 high-dose group and methotrexate group, while the levels of TGF - β and B7-1 (sCD80) in all drug treatment groups were increased in varying degrees (P < 0.05), and the most obvious increase was in senden-4 high-dose group and methotrexate group. Compared with the model group, the CTLA-4 IOD value of each group was significantly lower (P < 0.05); compared with the model group, the CTLA-4 IOD value of each drug treatment group was increased in varying degrees (P < 0.05), and the increase of senden-4 high-dose group and methotrexate group was the most obvious. Compared with the normal group, the CD80 IOD value of the model group was significantly increased (P < 0.05); compared with the model group, the B7-1 IOD value of each drug treatment group was decreased in varying degrees (P < 0.05), especially in the senden-4 high-dose group and methotrexate group. Conclusion The mechanism that Senden-4 alleviates rheumatoid arthritis could be related with the immunosuppressive response mediated by CTLA-4/B7-1,so as to treat CIA rats.
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