矽肺大鼠肺内淋巴管增生与纤维化进程的关系  

Relationship Between Lymphatic Hyperplasia and Fibrosis Process in Silicotic Rats

作　　者：刘微 刘和亮 张秀峰 郝小惠 郭志义 郭灵丽 王宏丽 

机构地区：[1]华北理工大学公共卫生学院,河北唐山063000 [2]华北理工大学医学实验研究中心,河北唐山063000

出　　处：《环境与职业医学》2016年第8期753-757,共5页Journal of Environmental and Occupational Medicine

基　　金：唐山市国际科技合作项目(编号:14160201B)

摘　　要：[目的]探讨矽肺发病过程中肺内淋巴管增生与纤维化进程的关系。[方法]56只Wistar大鼠随机分为矽肺模型组和对照组,模型组又按动物处死时间分为1、7、14、28、42和56 d 6个亚组,每组8只大鼠。采用墨汁-硝酸银染色观察淋巴管增生情况,实时荧光定量PCR方法检测VEGFR-3 m RNA转录水平,免疫组化法、比色法检测肺组织中I型胶原表达及羟脯氨酸含量。[结果]与对照组相比,矽肺大鼠肺组织中I型胶原从染尘后1 d、羟脯氨酸含量从染尘后7 d即开始升高(P<0.05或P<0.01);从染尘7 d开始发现增生的淋巴管,且随着染尘时间的延长,淋巴管增生呈现先增多后减少的趋势;VEGFR-3 m RNA表达在染尘后7 d开始增加(P<0.01)。Pearson相关性分析显示在染尘早期,即28 d以前,I型胶原含量、羟脯氨酸含量与VEGFR-3水平呈正相关(r=0.974 4,P=0.025 6;r=0.998 5,P=0.001 5),染尘28 d后I型胶原含量、羟脯氨酸含量与VEGFR-3水平呈负相关(r=-0.975 1,P=0.024 9;r=-0.974 4,P=0.025 7)。[结论]矽肺大鼠发病过程中出现肺组织淋巴管增生,其增生程度与矽肺纤维化具有相关性。[ Objective ] To assess relationship between lymphatic hyperplasia and fibrosis process in silicosis pathogenesis. [ Methods ] Fifty-six Wistar rats were randomly divided into control and silicosis model group. The silicosis model group was further divided into subgroups as 1, 7, 14, 28, 42, and 56d by animal neutralization time, eight rats in each group. Ink-silver nitrate staining was used to observe lymphatic hyperplasia. The level of mRNA transcription of vascular endothelial growth factor receptor-3 （VEGFR-3） was determined by real-time quantitative PCR; the levels of collagen I and hydroxyproline （HYP） were detected by fluorescence and immunohistochemistry staining. [ Results ] Compared with the control group, collagen I in the lung tissue rose up significantly from 1 d （P〈 0.05） and HYP from 7 d （P〈 0.01） after silica exposure. Pulmonary lymphatics hyperplasia was found in the silicotic rats after 7 d of silica exposure, and along with the extension of exposure time, it was increased first and then decreased. The mRNA expression of VEGRF-3 was increased significantly from 7 d （P 〈 0.01） after silica exposure. The results of Pearson correlation analysis showed that the contents of collagen I and HYP were positively correlated with the level of VEGRF-3 before 28 d of silica exposure （r=0.974 4, P=0.025 6; r=0.998 5, P=0.0015） and negatively after 28 d （r=-0.975 1, P=0.024 9; r=-0.974 4, P=0.025 7）. [ Conclusion ] Lymphatic hyperplasia occurs in lung tissue during the process of silicosis, and the severity is associated with silicotic fibrosis process.

关 键 词：矽肺纤维化 淋巴管增生 血管内皮生长因子受体-3 I型胶原 羟脯氨酸 

分 类 号：R114[医药卫生—卫生毒理学] R135[医药卫生—公共卫生与预防医学]