Hu G-X, Yao S-T, Zeng L-H, Peng Y-Z, Zheng J
Peking University Shenzhen Hospital, Shenzhen, China.
Peking University Shenzhen Hospital, Shenzhen, China
Genet Mol Res. 2015 May 4;14(2):4625-32. doi: 10.4238/2015.May.4.21.
The aim of this study was to investigate the effects of hydroxycamptothecin (HCPT) on the expression of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-1), and type I collagen in the lung tissue of rats with pulmonary fibrosis induced by bleomycin A5. We used hematoxylin eosin staining to observe the degree of pulmonary fibrosis in rats; Masson staining, reverse transcription polymerase chain reaction, and immunohistochemistry were used to observe the expression of collagen, MMP-1, and TIMP-1, and type I collagen. The expression of MMP-1 in the model group decreased significantly, while the expression of TIMP-1 and type I collagen significantly increased. After treatment with HCPT, the degree of pulmonary fibrosis and the expression of TIMP-1 and type I collagen decreased in all treatment groups. However, the expression of MMP-1 increased in a dose-dependent manner. Our results showed that HCPT decreased the pulmonary fibrosis induced by bleomycin A5 in rats, and an increase in MMP-1 expression and decrease in the TIMP-1 and type I collagen expression may be the mechanism that regulates the metabolism of the extracellular matrix.
本研究旨在探讨羟基喜树碱（HCPT）对博来霉素A5诱导的大鼠肺纤维化模型肺组织中基质金属蛋白酶-1（MMP-1）、MMP-1组织抑制剂（TIMP-1）及Ⅰ型胶原蛋白表达的影响。采用苏木精-伊红染色观察大鼠肺纤维化程度；采用Masson染色、逆转录聚合酶链反应及免疫组化法观察胶原蛋白、MMP-1、TIMP-1及Ⅰ型胶原蛋白的表达。模型组MMP-1表达显著降低，而TIMP-1及Ⅰ型胶原蛋白表达显著升高。HCPT治疗后，各治疗组肺纤维化程度及TIMP-1和Ⅰ型胶原蛋白表达均降低。然而，MMP-1表达呈剂量依赖性增加。我们的结果表明，HCPT可减轻博来霉素A5诱导的大鼠肺纤维化，MMP-1表达增加及TIMP-1和Ⅰ型胶原蛋白表达降低可能是调节细胞外基质代谢的机制。
