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目的探讨白介素-1受体拮抗剂(IL-lra)对实验性新月体肾炎肾脏组织骨调素(OPN)表达的调节作用,进一步阐明IL-1在实验性新月体肾炎发病机制中的作用。方法加速型实验性新月体肾炎模型应用兔抗鼠肾小球基底膜肾毒血清制备。第1组为模型组:注射肾毒血清后第0~7天,不加任何干扰治疗;另外2组为治疗组及治疗对照组:从第7~14天,分别给予IL-lra和生理盐水持续静脉点滴。结果模型组OPN的表达显著增高。生理盐水治疗组,OPN在肾小球和小管-间质细胞的表达更高,并和巨噬细胞的局部浸润及肾功能密切相关。而IL-lra治疗组,OPN的表达显著下调,巨噬细胞浸润明显减少,部分逆转肾功能。结论应用IL-lra抑制IL-1的活性可显著下调骨调素的表达和保护肾功能,提示IL-lra的治疗作用可能是通过抑制骨调素的表达,减少巨噬细胞在肾脏局部浸润的机制。
Objective To investigate the regulatory effect of interleukin-1 receptor antagonist (IL-lra) on osteopontin (OPN) expression in experimental crescentic nephritis and to further elucidate the role of IL-1 in the pathogenesis of experimental crescentic nephritis effect. Methods Accelerated experimental crescentic glomerulonephritis model was prepared by rabbit anti-mouse glomerular basement membrane nephrotoxic serum. The first group was model group: 0 ~ 7 days after injection of nephrotoxic serum, without any interference treatment; the other two groups were treated group and control group: from the 7th to the 14th day, were given IL-lra and saline Continuous intravenous drip. Results The expression of OPN in model group was significantly increased. In the saline treatment group, the expression of OPN was higher in glomerulus and tubule-stromal cells, and was closely related to the local infiltration and renal function of macrophages. In the IL-lra treatment group, the expression of OPN was significantly down-regulated, macrophage infiltration was significantly reduced, partially reversed renal function. Conclusions The inhibition of IL-1 activity by IL-1ra significantly down-regulated the expression of osteopontin and the protection of renal function, suggesting that the therapeutic effect of IL-1ra may be through the inhibition of osteopontin expression and local macrophage infiltration in the kidney mechanism.