| 摘要: |
| 目的:观察甲磺酸伊马替尼(以下简称伊马替尼)对博莱霉素诱导的小鼠肺纤维化的干预作用,并探讨其可能的作用机制。方法:C57BL/6小鼠随机分为对照组、模型组、地塞米松组和伊马替尼组(n=30)。采用博莱霉素制备小鼠肺纤维化模型,分别于术后第7、14、21天各处死10只小鼠,免疫组化半定量分析各组肺组织转化生长因子β1(TGF-β1)、基质金属蛋白酶 1(MMP-1)、基质金属蛋白酶抑制剂 1 (TIMP-1)表达的变化,并作相关性分析。结果:与模型组比较,伊马替尼组、地塞米松组肺组织TIMP-1、MMP-1、TGF-β1表达均降低(P<0.01)。TIMP-1表达与TGF-β1呈正相关(r=0.243,P=0.004)；除正常对照组外,其余3组MMP-1表达与TIMP-1表达呈负相关(r=-0.291,P＜0.000 1)。结论:甲磺酸伊马替尼可能通过下调TGF-β1抑制TIMP-1表达,从而相对上调MMP-1,维持TIMP-1/MMP-1平衡,抑制博莱霉素诱导的小鼠肺纤维化,作用效果与地塞米松类似。 |
| 关键词: 甲磺酸伊马替尼；博莱霉素 肺纤维化；转化生长因子β 基质金属蛋白酶1 基质金属蛋白酶抑制剂1 |
| DOI：10.3724/SP.J.1008.2009.0645 |
| 投稿时间：2008-11-23修订日期：2009-04-02 |
| 基金项目:上海市科委科研基金(06411963). |
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| Imatinib mesylate inhibits bleomycin-induced pulmonary fibrosis in mice: the mechanism |
| LI Li1,2, LI Yan-qin2* |
| (1.Shanghai Pulmonary Hospital,Tongji University,Shanghai 200433,China;2.Department of Respiratory, Renji Hospital, Medical College, Shanghai Jiaotong University, Shanghai 200127) |
| Abstract: |
| Objective:To observe the effect of imatinib mesylate on pulmonary fibrosis (PF) induced by bleomycin in mice and to explore the related mechanism. Methods: Totally 120 C57BL/6 mice were evenly randomized into control group, model group, dexamethasone group and imatinib group. The pulmonary fibrosis model was established using a single intratracheal infusion of bleomycin; the corresponding drugs were given to mice in each group. Ten mice was sacrificed in each group on day 7,14, and 21 after operation, respectively. The expression of matrix metalloproteinase 1(MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1(TGF-β1) in the lung tissues was semi-quantitatively analyzed by immunohistochemistry method. Results: Immunohistochemistry results showed that the expression of TIMP-1,MMP-1, and TGF-β1 in lung tissues of the dexamethasone group and imatinib group was significantly lower than that in the model group(P<0.01). There was a positive correlation between TGF-β1 and TIMP-1 expression(r=0.243,P=0.004). A negative correlation was found between MMP-1 and TIMP-1 in all the other 3 groups other than in the normal control group(r=-0.291,P＜0.000 1). Conclusion: Imatinib may downregulate TGF-β1 expression, inhibit TIMP-1 expression, and upregulate MMP-1 expression, maintaining the balance of TIMP-1/MMP-1,subsequently inhibit the development of pulmonary fibrosis, showing a similar effect of dexamethasone. |
| Key words: imatinib mesylate bleomycin pulmonary fibrosis transforming growth factor β matrix metalloproteinase 1 tissue inhibitors of metalloproteinase 1 |
