赖氨酰氧化酶样蛋白-2在肺纤维化小鼠中的表达及意义  

The expression and significance of lysyl oxidase like-2 in pulmonary fibrosis mice

作　　者：白羽[1] 郑毅[1] 

机构地区：[1]首都医科大学附属北京朝阳医院风湿免疫科,100020

出　　处：《中华风湿病学杂志》2015年第9期606-610,I0001,共6页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（81471616）

摘　　要：目的 研究在肺纤维化小鼠中,赖氨酰氧化酶样蛋白-2（LOXL2）在临床前期对疾病发生和疾病活动期对病情进展的预测价值,及其与TGF-β1的关系.方法 50只雄性C57BL 6小鼠按随机数字表法分为对照组、模型组,模型组建立博莱霉素诱导的肺纤维化模型,分别于给药第3、7、14、28天观察小鼠肺部病变,ELISA法检测血清及肺组织匀浆LOXL2及肺组织匀浆TGF-β1,组间数据比较采用单因素方差分析或非参数秩和检验,两因素间关系采用Spearman相关分析.结果 ①模型组小鼠血清及肺组织匀浆LOXL2水平高于对照组[（56±48）与（25±23）,P＜0.05;（61±32）与（22±16）,P＜0.05],且与影像学评分,病理炎症、纤维化评分呈正相关（血清：相关系数分别为0.435,0.533,0.335,P＜0.05;肺组织匀浆：相关系数分别为0.675,0.736,0.526,P＜0.05）.②模型组小鼠肺组织匀浆TGF-β1水平较对照组升高[（302±197）与（64±16）,P＜0.05],肺组织匀浆LOXL2与TGF-β1水平呈正相关（相关系数为0.520,P＜0.05）.结论 LOXL2参与博莱霉素诱导的肺纤维化病变,是潜在的肺纤维化临床前期及病情进展时的血清学标志物,其水平升高可能与TGF-β 1有关,共同作用于肺纤维化病变.Objective To assess whether lysyl oxidase like-2 （LOXL2） has a predictive or prognostic value in pulmonary fibrosis mice,and identify the relationship between LOXL2 and transforming growth factor （TGF）-β 1.Methods Male C57BL/6 mice （n=50） were randomly divided into the experimental group （n=40） and controls （n=10）.Each mouse in the experimental group was induced by injecting bleomycin into trachea and mice were sacrificed on day 3,7,14 and 28,respectively.The concentrations of LOXL2,TGF-β 1 of the serum and lung homogenates were measured by enzyme-linked immunosorbent assay.One-factor analysis of variance （ANOVA） and nonparametric rank sum test was used for the comparisons between the two groups.Associations between these factors were analyzed by Spearman＆#39;s test.Results ① The levels of serum and lung homogenates LOXL2 in the experimental group were obviously increased as compared to those in the controls [serum：（56±48） vs （25±23）,P〈0.05;lung homogenates：（61±32） vs （22±16）,P〈0.05].And in the experimental group,a positive correlation was found between the level of LOXL2 and the radiological index,the pathological score of inflammation and fibrosis.（Serum：r=0.435,0.533,0.335,P〈0.05;lung homogenates：0.675,0.736,0.526,P〈0.05）.② The levels of lung homogenates TGF-β 1 in the experimental group were obviously increased as compared to those in the controls [（302±197） vs （64±16）,P〈0.05].A positive correlation was found between the level of lung homogenates LOXL2 and the level of lung homogenates TGF-β1 （r=0.520,P〈0.05）.Conclusion LOXL2 participates in the pathological process of bleomycin induced pulmonary fibrosis in mice.It predicts pulmonary fibrosis in the preclinical stage and is associated with increased risk for disease progression.The elevated levels of LOXL2 and TGF-β 1 may have some relationship.They both are involved in the disease progression of pulmonary fibrosis.

关 键 词：赖氨酰氧化酶样蛋白-2 博莱霉素 肺纤维化 转化生长因子Β 

分 类 号：R563[医药卫生—呼吸系统]