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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 mesylate (hereinafter referred to as imatinib) on bleomycin-induced pulmonary fibrosis in mice and to explore its possible mechanism. Methods: C57BL / 6 mice were randomly divided into control group, model group, dexamethasone group and imatinib group (n = 30). Bleomycin was used to prepare mouse model of pulmonary fibrosis, and 10 mice were sacrificed on the 7th, 14th and 21st day after operation respectively. Immunohistochemical semiquantitative analysis of the expression of transforming growth factor-β1 (TGF-β1) , Matrix metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected and analyzed. Results: Compared with the model group, the expressions of TIMP-1, MMP-1 and TGF-β1 in lung tissue of imatinib group and dexamethasone group were decreased (P <0.01). The expression of TIMP-1 was positively correlated with TGF-β1 (r = 0.243, P = 0.004). The expression of TIMP-1 in the other three groups was negatively correlated with the expression of TIMP-1 ). CONCLUSION: Imatinib mesylate inhibits the bleomycin-induced pulmonary fibrosis in mice by down-regulating the expression of TIMP-1 by downregulating the expression of TIMP-1, thereby up-regulating MMP-1, maintaining the balance of TIMP-1 / MMP- , The effect is similar to dexamethasone.