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国产白细胞介素-1受体阻滞剂对胶原性关节炎大鼠淋巴细胞及巨噬细胞功能的影响

Effects of interleukin-1 receptor antagonist on lymphocyte and macrophage of rats with collagen-induced arthritis

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【作者】 吴丽; 张玲玲; 孙妩弋; 汪倪萍; 王华; 岳莉; 魏伟;

【Author】 WU Li, ZHANG Ling-ling, SUN Wu-yi, WANG Ni-ping, WANG Hua, YUE Li, WEI Wei (Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China)

【机构】 安徽医科大学临床药理研究所; 安徽医科大学临床药理研究所 合肥 230032; 合肥 230032; 合肥 230032;

【摘要】 目的:观察国产白细胞介素-1受体阻滞剂(IL-1ra)对大鼠胶原性关节炎(CIA)的影响。方法:鸡Ⅱ型胶原诱导大鼠CIA模型,关节评分法观察关节炎的发生情况;3H-TdR掺入法检测T细胞、B细胞增殖反应;采用小鼠淋巴细胞增殖法检测IL-1活性;放免法检测大鼠腹腔巨噬细胞(PMφ)培养上清液肿瘤坏死因子(TNF)和前列腺素E2(PGE2)的含量。结果:CIA大鼠在致炎后d10,出现关节红肿,刀豆蛋白(ConA)或脂多糖(LPS)诱导的T和B淋巴细胞增殖反应增强;PMφ产生IL-1,TNF-α,PGE2的水平升高。IL-1ra(7.5,30,120mg·kg-1·d-1)和阳性对照组(anakinra 120mg·kg-1·d-1)sc,连续7d,均能减轻CIA大鼠关节局部炎症,降低关节评分;IL-1ra(30,120mg·kg-1·d-1)能明显降低CIA大鼠过高的T淋巴细胞增殖反应,IL-1ra(7.5,30,120mg·kg-1·d-1)能明显降低CIA大鼠B淋巴细胞增殖反应;降低CIA大鼠PMφ产生过高的IL-1,TNF-α及PGE2水平。结论:IL-1ra对CIA大鼠淋巴细胞和巨噬细胞的增殖反应具有抑制作用。

【Abstract】 Objective:To investigate protections of interleukin-1 receptor antagonist (IL-lra) against collagen-induced arthritis (CIA) in rats. Methods: A CIA model was set up in SD rats by subcutaneous injection with type II collagen. The severity of arthritis was rated with arthritis scores. The examination of conA-and lipid polysaccharide (LPS)-induced splenocytes proliferation and interleukin-1 (IL-1) activities were conducted using a 3H-TdR intake method. Tumor necrosis factor alpha (TNF-α) and PGE2 in the culture broth of macrophage (PMΦ) were quantified using radioimmunoassay. Results: The conA or LPS increased the level of T-and B-lymphocyte in 10 days after CIA in rats. The local inflammatory symptoms and B lymphocytes proliferation were reduced after subcutaneous injection with IL-lra at 7.5,30 and 120mg·kg-1·d for 7 days, and T lymphocyte proliferation was suppressed when IL-lra at 30 and 120mg·kg-1·d-1 was s. c. given in rats with CIA. The IL-1, TNF-α and PGR2 levels in the PMΦ were inhibited by IL-1ra. Conclusion: IL-1ra inhibits the proliferation of lymphocytes and macrophage in the CIA rats.

【基金】 安徽省教育厅资助项目(2004kj217)
  • 【文献出处】 中国新药杂志 ,Chinese New Drugs Journal , 编辑部邮箱 ,2005年03期
  • 【分类号】R96
  • 【被引频次】4
  • 【下载频次】137
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