【摘要】 目的探讨白细胞介素13(IL-13)在急性肺损伤/肺纤维化发病过程中的作用,并试图阐明IL-13可能通过转化生长因子(TGF)β1途径致肺纤维化。方法选择健康雄性Wister大鼠,经气管一次性灌注博来霉素(BLM)建立急性肺损伤/肺间质纤维化模型。对照组气管内灌注无菌生理盐水。分别于给药后第1、3、7、14、28天处死动物。右肺行支气管肺泡灌洗(BAL),留取支气管肺泡灌洗液(BALF),计数BALF细胞总数,并用HE染色方法计数细胞分数。用免疫组织化学技术,在显微镜下计数BALF中IL-13和TGFβ1免疫阳性细胞百分数。右肺组织匀浆后测羟脯氨酸(HYP)含量。结果肺组织HE染色显示BLM第7天肺泡腔内有大量炎性细胞浸润,第28天时肺泡结构破坏,出现斑片状纤维组织灶。BLM第14天时HYP含量较盐水组显著增加,第28天时达最高值。IL-13、TGFβ1在BALF中的巨噬细胞(AM)、嗜酸细胞及淋巴细胞上均有表达,在博莱霉素组表达增强。其中BLM第7天时IL-13、TGFβ1表达阳性的AM百分数最高,而且两者阳性细胞百分数呈正相关(r=0.86,P<0.05)。结论IL-13与肺纤维化关系密切,IL-13在急性肺损伤期主要来源于AM。IL-13可能通过TGFβ1途径发挥致肺纤维化作用。更多还原

【Abstract】 [Objective] To investigate the potential roles of IL-13 during the process of acute pulmonary injury and fibrosis with a rat model of bleomycin-induced pulmonary fibrosis. To try to elucidate that macrophage is the dominant cell to secret IL-13, and IL-13 probably induce tissue fibrosis by selectively stimulating and activating transforming growth factor β1 (TGFβ1). [Methods] Wister rats were divided into 6 groups of 10 rats each, with each group further subdivided equally between control and experimental or bleomycin-treated groups which was killed at days 1, 3, 7, 14 and 28 after bleomycin or saline endotracheal. At each time point, the right lungs were lavaged with saline at 37℃, then differential cell counts were performed and hydroxyproline (HYP) in right lung tissues were determined. Immunohistochemistry assays for IL-13, TGFβ1 were performed in the cells in bronchial alveolar lavage fluid (BALF). [Results] HE staining showed that BLM group at days 7 stimulates a great deal of inflammatory cells infiltration into the alveolar, and at days 28, the alveolar structure was obviously destroyed, which was charactered with tissue fibrosis focus. HYP levels in BLM group were significantly increased at days 14 and prominated at days 28 compared with the control group. Immunohistochemical staining showed that IL-13, TGFβ1 were localized in alveolar macrophages, eosinophiles and lymphocytes in both BLM groups and control groups. However, overall intensity of IL-13 TGFβ1 expression in BLM groups was stronger than that in the controls. At BLM days 7 group, the percentage of positive stained cells of IL-13, TGFβ1 reached the highest level at days 28, respectively. Furthermore, the percentage of IL-13 staining cells was positively correlated with the percentage of TGFβ1 cells. [Conclusion] At the lung-injuring stage, the potential resource of IL-13 is alveolar macrophage. The fibrogenic effects of IL-13 are mediated, in some extent, by TGFβ1 pathway.更多还原