摘要
目的 :观察白细胞介素 18(interlenkin ,IL 18)在博莱霉素致大鼠肺纤维化模型中的表达 ,探讨其在肺纤维化发病机制中的作用。方法 :雄性Wistar大鼠分为 3组 :博莱霉素模型组 30只 ,气管内一次性注入博莱霉素A55mg·kg 1,分别于第 1、3、7、14、2 8天各处死 6只 ;阿奇霉素治疗组 12只 ,气管内注入博莱霉素后 2h开始于胃管内给阿奇霉素 (80mg·kg 1·d 1,每周 3次 )治疗 ,分别于第 7、2 8天各处死 6只 ;对照组 6只 ,气管内及胃管内均给生理盐水 ,第 7天处死。对HE染色病理结果进行计算机灰度扫描半定量分析 ,用RNA酶保护实验的方法检测IL 18mRNA的表达 ,用免疫组织化学方法检测肺组织IL 18蛋白的表达。结果 :IL 18在正常肺组织有一定水平的表达 ,自气管内注入博莱霉素第 1天开始迅速升高 ,至第 7天达高峰后逐渐下降 ,第 2 8天时仍高于正常。经阿奇霉素有效抗炎治疗后 ,其表达明显下降。免疫组织化学显示活化的肺泡巨噬细胞和间质单核细胞是IL 18的主要来源 ,某些细支气管上皮细胞、肺泡上皮细胞和纤维化严重区域的成纤维细胞也有表达。结论 :IL 18是肺纤维化中重要的前炎症因子 ,不仅参与早期的肺损伤和炎症的维持、发展 ,也可能参与纤维化的形成。阿奇霉素可抑制IL
Objective:To observe the expression of IL-18 in bleomycin-induced pulmonary-fibrosis in rats and discuss its possible role in the pathogenesis of pulmonary fibrosis. Methods:the male Wistar rats were divided into three experimental groups randomly:after intratracheal instillation of single dose bleomycin A5 (BLM) 5 mg·kg -1, normal saline was given by oral gavage daily in the 30 bleomycin treated rats (BLM groups) and they were sacrificed on day 1, 3, 7, 14, 28 separately; After intratracheal instillation of BLM, azithromycin(AZI) was given by oral gavage in a daily dose of 80 mg·kg -1, 3 days/week in the 12 AZI treated rats(AZI group) and they were sacrificed on day 7, 28 separately; the 6 rats of control group were given normal saline and sacrificed on day 7. The quantitative analysis of histopathologic changes among the three groups was performed by computer gray scan. We examined the expression of IL-18 mRNA by RNase protection assay (RPA). Immunohistochemistry was performed to investigate the expression of IL-18 protein in the lung. Results:IL-18 is expressed in normal lung tissue in certain level. After intratracheal instillation of BLM, the expression of IL-18 mRNA significantly increased rapidly from day 1, reached peak on day 7, than decreased gradually and still more than normal level on day 28(vs control,P<0.01). There was the similar trend in the expression of IL-18 protein. After the effective therapy of Azithromycin, its expression decreased significantly. Activated alveolar macrophages and monocytes in pulmonary interstitial are the main source of IL-18. Some bronchiolar epithelial cells, alveolar epithelial cells and fibroblasts in the area of serious fibrosis also expressed IL-18.Conclusion:IL-18 is an important proinflammatory cytokine in pulmonaryfibrosis. It may not only participate the lung injury in the early stage and involve in the development of the inflammatory reaction in pulmonary fibrosis. Azithromycin can inhibit the expression of IL-18 in the lung of bleomycin-induced pulmonary-fibrosis in rats.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2002年第4期376-379,383,共5页
Journal of Peking University:Health Sciences
