尿激酶型纤溶酶原激活物(u-PA)基因对小鼠实验性肺气肿的影响及其机制

The role of urokinase type plasminogen activator gene in mouse experimental emphysema

目的研究尿激酶型纤溶酶原激活物(u-PA)基因对小鼠实验性老年性肺气肿样改变的影响及其机制。方法取15d及4月龄野生型小鼠和u-PA基因敲除小鼠肺组织,HE、Weigert弹力纤维染色比较不同基因型小鼠肺组织形态,Image Pro Plus软件分析u-PA基因缺失对肺组织弹力纤维蛋白含量的影响,并采用Real-time PCR检测肺组织间质成份表达水平。结果15d鼠龄u-PA基因缺失小鼠相比野生型(WT)小鼠肺组织形态无明显差异;弹力纤维含量、弹力蛋白基因表达、MMP-12基因表达无显著差异;4月龄u-PA基因缺失小鼠肺泡壁结构较野生型小鼠完整,肺泡腔无明显增大;肺泡弹力纤维含量、肺组织弹力蛋白基因表达及TIMP-1基因的表达显著高于野生型小鼠,MMP-12基因表达也略有增高。结论u-PA基因缺失能够减轻小鼠实验性老年性肺气肿样改变,其分子机制可能是u-PA基因缺失后,弹力蛋白和TIMP-1基因的表达增加,导致肺组织弹力纤维含量增加。

Objective To observe the role of urokinase type plasminogen activator （u-PA） gene in mice experimental senile emphysema changes and its possible mechanism. Methods Wild type （WT） mice and u-PA gene knock out （KO） mice were fed under the criterion of SPF. At 15th day and 4th month, mice were anaesthetised and anatomized for further experiments. Part of mice lung was pre- pared for HE and weigert staining, another parts of lung were picked for real- time PCR. Results 15th day old WT and u-PA gene KO mice had similar lung alveolar structure. The content of elastin, elastin mRNA, MMP-12 mRNA in the lung had no significant difference between these two genotype mice. With aging, 4th month old u-PA gene KO mice had more integrated alveolar cavity. The elastin appears to be higher than that of WT mice. The elastin and TIMP-1 gene expression levels increased greatly in u-PA gene KO mice. Conclusions Disruption of u-PA gene might protect the lung alveolar structure through increasing elastin by enhancing the elastin and TIMP-1 gene expression.