百草枯致小鼠肺间质纤维化过程中Smad3蛋白的表达

摘要

Objective The expression of Smad3 protein in the pulmonary fibrosis induced by paraquat (PQ) was detected by immunohistochemistry. Methods 57BL/6J male mice (n = 58)were divided randomly into the experimental group and control group. Pulmonary fibrosis was induced by intraperitoneal injection of PQ(10 mg/kg)in the experimental group(n = 48) , while physiological saline was used in the control group(n = 10) by the same method. The mice were sacrificed on days 2,5,7 and 14 in the experimental group and the control ones on day 7. The lungs were taken for histo-logical examinatioon using HE staining and the expression of Smad3 protein was determined by immunohistochemistry. Results The histological changes including edema, hemorrhage and inflammatory cell infiltration were seen in the lung tissues of mice after PQ administration on days 2 and 5. There were slight collagen deposition and plaque-like fibrosis on day 7 and apparent fibrosis on day 14. The Smad3-positive signs appeared in the nucli of infiltrating macrophages and many type II alveolar epithelial cells on days 2, 5 and 7. The positive expression of Smad3 proteins was positively correlated with the amount of infiltrating macrophages. On day 14 the faint Smad3-positive expression was detected in the nuclei of fibroblasts in hyperplastic foci. Conclusions The expression of Smad3 protein is abnormal during pulmonary fibrosis induced by PQ and Smad3 plays an important role in the development of pulmonary fibrosis.%目的 使用免疫组织化学的方法观察百草枯(paraquat,PQ)致小鼠肺间质纤维化过程中Smad3蛋白的表达.方法 58只雄性C57BL/6J小鼠随机分组.实验组48只,通过腹腔注射10 mg/kg PQ建立小鼠肺间质纤维化模型,对照组10只,腹腔注射等量生理盐水.小鼠在实验组染毒后第2、5、7、14天和对照组第7天时分别被安乐死,留取肺组织标本.标本进一步进行HE染色和Smad3蛋白的免疫组化研究.结果 光镜观察小鼠染毒后第2～5天肺组织出现水肿、出血、炎症细胞浸润等改变,第7天有少量胶原沉积及斑片状的纤维化表现,第14天表现更加明显.免疫组化观察染毒小鼠肺组织Smad3蛋白表达,第2～7天肺中巨噬细胞和部分Ⅱ型肺泡上皮细胞的细胞核中见到阳性表达.Smad3阳性表达和巨噬细胞数量呈正相关.第14天,在成纤维细胞灶增生的成纤维细胞核中,也可见到Smad3弱阳性表达.结论 在PQ致肺间质纤维化过程中,Smad3蛋白异常表达并对肺纤维化的发生发展具有重要的作用.