Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, PR China.
Mol Med Rep. 2013 Jan;7(1):149-53. doi: 10.3892/mmr.2012.1140. Epub 2012 Oct 22.
The aim of this study was to observe the effect of antisense tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) cDNA on the concentration of hydroxyproline (HYP) and the expression of TIMP-1 and matrix metalloproteinase-2 (MMP-2) in the lung tissue of rats with bleomycin (BLM)‑induced pulmonary fibrosis. Sprague-Dawley rats were randomly divided into 5 groups: the control, pulmonary fibrosis model, sense TIMP-1 transfection, antisense TIMP-1 transfection and empty vector transfection groups. For the transfection groups, following the intratracheal injection of BLM on days 1, 3, 7, 14, 28 and 60, the rats were treated with retroviral vectors and sacrificed on day 28. The control and pulmonary fibrosis groups were treated with normal saline at the same time‑points. The concentration of HYP and the expression levels of TIMP-1 and MMP-2 in the lung tissue were detected. The HYP concentration and lung tissue TIMP-1 expression levels of the antisense TIMP-1 group decreased significantly on days 1 and 3 compared with those of the empty vector and pulmonary fibrosis groups at the same time-points (P<0.01), but increased significantly in the sense TIMP-1 group (P<0.01). No significant differences were observed in the HYP concentration and TIMP-1 expression levels in the antisense TIMP-1, sense TIMP-1, empty vector and pulmonary fibrosis groups on days 7, 14, 28 and 60. The lung expression levels of MMP-2 in all groups, with the exception of the control group, had no significant differences at all time-points (P>0.05). Antisense TIMP-1 cDNA retroviral vectors are able to suppress the development of pulmonary fibrosis in the early stages.
本研究旨在观察反义组织金属蛋白酶抑制剂-1（TIMP-1）cDNA 对博莱霉素（BLM）诱导的肺纤维化大鼠肺组织羟脯氨酸（HYP）浓度和 TIMP-1、基质金属蛋白酶-2（MMP-2）表达的影响。Sprague-Dawley 大鼠随机分为 5 组：对照组、肺纤维化模型组、正义 TIMP-1 转染组、反义 TIMP-1 转染组和空载体转染组。转染组于第 1、3、7、14、28 和 60 天经气管内注射 BLM 后，给予逆转录病毒载体，并于第 28 天处死。对照组和肺纤维化组同时给予生理盐水处理。检测肺组织 HYP 浓度和 TIMP-1、MMP-2 表达水平。反义 TIMP-1 组在第 1、3 天 HYP 浓度和肺组织 TIMP-1 表达水平明显低于同时点空载体组和肺纤维化组（P<0.01），但明显高于正义 TIMP-1 组（P<0.01）；反义 TIMP-1、正义 TIMP-1、空载体和肺纤维化组在第 7、14、28 和 60 天 HYP 浓度和 TIMP-1 表达水平无明显差异。各组 MMP-2 肺组织表达水平除对照组外，各时间点均无明显差异（P>0.05）。反义 TIMP-1 cDNA 逆转录病毒载体能够抑制肺纤维化的早期发展。
