中文摘要：

目的观察N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸（Ac-SDKP）和血管紧张素转换酶（ACE）/血管紧张素Ⅱ（AngⅡ）/血管紧张素Ⅱ1型受体（AT1R）轴在大鼠矽肺纤维化发生、发展过程中的表达变化及其对矽肺纤维化形成的影响。方法 60只雄性Wistar大鼠随机分为6组（n=10）,分别染尘0、2、4、8、12、16周构建大鼠矽肺模型。HE染色观察肺组织形态,Western blotting检测矽肺大鼠肺组织中α-平滑肌肌动蛋白（α-SMA）、Ⅰ型胶原（ColⅠ）、纤连蛋白（Fn）、ACE及AT1R蛋白的表达,ELISA法检测矽肺大鼠肺组织中Ac-SDKP和AngⅡ的含量。结果 HE染色结果显示,大鼠染尘2周后即可见肺泡壁增宽及巨噬细胞浸润,4周组偶见孤立的细胞性结节形成（主要由巨噬细胞构成）,8周组和12周组大鼠肺泡间隔增宽明显,且细胞性结节数量增多,16周组肺组织内可见多个细胞性结节的融合和间质纤维化的形成,并可见细胞纤维性矽结节的形成。与对照组比较,矽肺模型4、8、12、16周组大鼠肺组织α-SMA、ColⅠ、Fn蛋白表达逐渐增高（P〈0.05）,2、4、8、12、16周组大鼠肺组织ACE、AngⅡ、AT1R蛋白表达逐渐增高（P〈0.05）,而大鼠肺组织中Ac-SDKP的表达水平在矽肺模型2周组明显高于对照组（P〈0.05）,随后逐渐降低,在12周和16周组已明显低于对照组（P〈0.05）。结论矽肺局部组织ACE/AngⅡ/AT1R的表达在矽肺发生、发展过程中逐渐升高,而Ac-SDKP的表达逐渐降低。Ac-SDKP和AngⅡ信号参与了大鼠矽肺纤维化的过程。

英文摘要：

Objective To investigate the changes of N-acetyl-seryl-aspartyl-lysyl-proline （Ac-SDKP） and angiotensin converting enzyme （ACE）/angiotensin Ⅱ （Ang Ⅱ ）/angiotensin Ⅱ type 1 receptor （AT1R） axis and their impact on the development and progression of silicotic fibrosis. Methods Sixty male Wistar rats were randomly divided into 6 groups （n=10）. The rats inhaled dust for 0, 2, 4, 8, 12, and 16 weeks （w） respectively to reproduce silicosis model. HE staining was performed to observe the pathological changes of the lung tissue. The expression of α smooth muscle actin （α-SMA）, collagen I （Col I ）, fibronectin （Fn）, ACE and ATIR were measured by Western blotting. The levels of Ac-SDKP and Ang Ⅱin lung tissue were detected by ELISA. Results Macrophage infiltration and widened alveolar wall were observed by HE staining in the silicosis 2-w group. Isolated cell lesions which composed of macrophages were seen in silicosis 4-w group. The alveolar wall widened obviously and the number of silicotic nodules increased at 8w and 12w. The fusion of silicotic lesions, interstitial fibrosis and fibrous lesions were observed at 16w. Compared with control group, the expressions of o~-SMA, Col I and Fn protein in silicosis 4-, 8-, 12-, and 16-w group increased gradually. In silicosis 2-, 4-, 8-, 12-, 16-w group, the expressions of ACE, Ang Ⅱ and ATIR gradually increased compared to the control. The level of Ac-SDKP in the lung tissue of silicosis 2-w group was significantly higher than that in control group, and then decreased gradually, and significantly lower in the silicosis 12- and 16-w group than the control （P〈0.05）. Conclusion Along with the development and progression of silicosis, ACE, Ang Ⅱ, and AT1R expressions gradually increase in local lung tissue, while the expression of Ac-SDKP gradually decreases. Ac-SDKP and Ang Ⅱ signal would participate the silicotic fibrosis process in rats.