N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸对基质金属蛋白酶-1和基质金属蛋白酶组织抑制因子-1的调节在大鼠矽肺纤维化形成中的作用

目的:探讨N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸(AcSDKP)对大鼠肺内基质金属蛋白酶-1(MMP-1)和基质金属蛋白酶组织抑制因子-1(TIMP-1)表达的调节在拮抗矽肺纤维化形成过程中的作用.方法:气管内灌注染尘法制作大鼠矽肺模型,将含有AcSDKP的微量药物释放泵埋入腹腔.实验动物随机分为矽肺模型对照4周组,矽肺模型对照8周组,矽肺模型4周组,矽肺模型8周组,抗纤维化治疗组及预防治疗组.H-E染色和免疫组织化学显色对矽肺纤维化病变和MMP-1和TIMP-1在肺组织内的表达进行形态学观察;免疫印迹法对肺内MMP-1和TIMP-1酶蛋白表达进行检测.结果:与模型对照组比较,矽肺大鼠肺内MMP-1和TIMP-1表达增强.与矽肺模型组比较,AcSDKP能够上调矽肺大鼠肺内MMP-1的表达,下调TIMP-1的表达,使MMP-1/TIMP-1的比值升高.结论:AcSDKP能够促进矽肺大鼠肺内MMP-1的表达,抑制TIMP-1的表达,从而加速了细胞外基质(包括胶原)的降解,这可能与AcSDKP抗矽肺纤维化的作用有关.

Effect of N-acetyl-seryl-aspartyl-lysyl-proline on expression of MMP-1 and TIMP-1 in the lung of rat with silicosis

Objective: To investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the expression of MMP-1 and TIMP-1 in the lung of rat with silicosis. Methods: The Wistar rats were intratracheally instilled with silica as silicotic models. Drug releasing pumps with AcSDKP were implanted in the abdominal cavity of the rats. Rats were divided into 6 groups randomly: control 4 weeks, control 8 weeks, silicotic model 4 weeks, silicotic model 8 weeks, anti-fibrosis treatment of AcSDKP and preventing fibrosis treatment of AcSDKP. The lung fibrosis and expression of MMP-1 and TIMP-1 were observed by H-E staining and immunohistochemistry;The expressions of MMP-1 and TIMP-1 protein in the lungs of the rats were evaluated by Western blot. Results: Compared with the control group, the expressions of MMP-1 and TIMP-1 were increased in the lungs of the rats with silicosis. Compared with the silicotic model group, AcSDKP up-regulated the expression of MMP-1, down-regulated the expression of TIMP-1 in the lungs of the rats with silicosis, and increased the MMP-1/TIMP-1 ratio. Conclusion: AcSDKP could stimulate the expression of MMP-1 and inhibit the expression of TIMP-1 in the lungs of rats with silicosis, and thus induce the extracellular matrix (including collagen) degradation, which is possibly related with anti-fibrosis effect of AcSDKP.