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<0.0001)。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。
Objective：To observe the effect of imatinib mesytate 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 bleomyein; 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 immunohlstochemistry 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.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2009年第6期645-650,共6页
Academic Journal of Second Military Medical University
基金
上海市科委科研基金(06411963)~~
