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山东大学学报(医学版)

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尿激酶对肺纤维化干预作用及对TGF-β1的影响

万兵1,郑金旭1,黄新建1,严玉兰1,吴建农2   

  1. 江苏大学附属医院 1.呼吸科; 2.病理科, 江苏 镇江 212001
  • 收稿日期:2007-05-28 修回日期:1900-01-01 出版日期:2007-12-24 发布日期:2007-12-24
  • 通讯作者: 郑金旭

Effect of Urokinase on bleomycin-induced pulmonary fibrosis and the expression of transforming growth factor-β1 in rats

WAN Bing1,ZHENG Jin-xu1,HUANG Xin-jian1,YAN Yu-lan1,WU Jian-nong2   

  1. 1. Department of Respiratory Diseases, 2. Department of Pathology,Affiliated Hospital, Jiangsu University, Zhenjiang 100730, Jiangsu, China
  • Received:2007-05-28 Revised:1900-01-01 Online:2007-12-24 Published:2007-12-24
  • Contact: ZHENG Jin-xu

摘要: 目的研究尿激酶型纤溶酶原激活剂(uPA)对肺纤维化模型的干预作用和对TGF-β1的影响。方法45只SD雄性大鼠随机分成3组,每组15只: (1)干预组:经气管灌注博莱霉素,随后从第2天起每两天腹腔给予尿激酶干预;(2)模型组:气管内灌注博莱霉素;(3)对照组:气管内滴入生理盐水。模型组与对照组腹腔给予生理盐水。所有动物第28天全部处死。肺组织经苏木精-伊红(HE)、Masson胶原染色来评价肺泡炎和肺纤维化。对肺泡灌洗液进行细胞计数、分类,酶联免疫吸附测定( ELISA)法检测灌洗液中TGF-β1含量。结果尿激酶干预组中性粒细胞百分比为(3.1±1.8),低于模型组(9.3±4.1),高于对照组(2.5±1.3),有统计学意义(P<0.01) 。干预组肺泡炎程度为(0.9±0.7)分,低于模型组(1.7±0.6)分,高于对照组(0.2±0.4)分,有统计学意义(P<0.01)。干预肺纤维化程度(1.1±0.7)分,低于模型组的(2.0±0.8)分(P<0.01)。干预组TGFβ1含量在第28天为(42.5±1.7)ng/mL,低于模型组的(45.6±0.6)ng/mL (P<0.01),差异有统计学意义。结论尿激酶能减轻博来霉素诱导的大鼠肺纤维化,可能通过抑制TGF-β1来实现

关键词: 博莱霉素, 转化生长因子β1 , 肺纤维化, 尿激酶

Abstract: Objective To study the effects of urokinase on bleomycininduced pulmonary fibrosis in rats and its possible mechanism. Methods 45 male SD rats were randomly divided into three groups: the model group, the control group and the urokinase treatment group. The rats were intratracheally instilled with bleomycin(5mg/kg)or sterile saline. From the second day after bleomycin or sterile saline challenge, by intraperitoneal injection every two days, the urokinase treatment group was given urokinase (27500U/kg), the other two groups were given sterile saline. All the rats were sacrificed on day 28. Histological changes of the lungs were determined by HE staining and Masson′s trichrome staining. The level of transforming growth factor-β1 in BALF was determined by ELISA. Results At day 28, the neutrophil proportion in BALF was 3.1±1.8 in the treatment group, which was significantly lower than that of the model group(9.3±4.1) and higher than that of the control group(2.5±1.3) (P<0.01);the score of alveolitis was 0.9±0.7 in the treatment group, which was significantly lower that in the model group (1.7±0.6) (P<0.01) but was higher than that in the control group(0.2±0.4) (P<0.05). The pulmonary fibrosis was significantly decreased in the treatment group compared with the model group [(1.1±0.7) vs (2.0±0.8), P<0.01). The transforming growth factor-β1 level in BALF in the treatment group also significantly decreased compared with the model group [(42.5±1.7)ng/ml vs (45.6±0.6), P<0.01). ConclusionsUrokinase alleviates the bleomycininduced pulmonary fibrosis in rats possibly by inhibiting the expressions of transforming growth factor-β1 in lung.

Key words: Urokinase, Pulmonary fibrosis, Bleomycin, Transforming growth factor-β1

中图分类号: 

  • R563.1+3
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