多西环素对哮喘大鼠血管内皮生长因子、基质金属蛋白酶9的作用及血管重塑的影响  

Effects of doxycycline on vascular endothelial growth factor,matrix metalloproteinases-9 and vascular remodeling in asthmatic rats

作　　者：韩雪娇 王亮[2] 杨红申[3] 侯宏伟[4] 李亚妹[5] 李香兰[6] 

机构地区：[1]河北省邢台市第三医院呼吸科,河北邢台054099 [2]河北省胸科医院呼吸科,河北石家庄050041 [3]河北医科大学第二医院呼吸科,河北石家庄050000 [4]河北省胸科医院感染科,河北石家庄050041 [5]河北省胸科医院护理部,河北石家庄050041 [6]河北省胸科医院急诊科,河北石家庄050041

出　　处：《河北医科大学学报》2015年第6期638-643,共6页Journal of Hebei Medical University

基　　金：河北省医学科学研究重点课题计划(20120248)

摘　　要：目的观察多西环素对哮喘大鼠血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶9(matrix metalloproteinases-9,MMP-9)表达的影响。探讨多西环素对哮喘气道重塑、血管重塑的作用。方法 33只雄性SD大鼠随机分为对照组、哮喘组、多西环素组各11只。将大鼠以1%戊巴比妥钠麻醉,取材。收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BLAF),计数细胞总数、中性粒细胞、淋巴细胞及嗜酸性粒细胞;部分肺组织行病理切片,HE染色;免疫组织化学法检测各组大鼠肺组织中VEGF和MMP-9的表达变化,并应用图像分析软件技术测量VEGF和MMP-9的相对表达强度;ELISA法检测血清中VEGF的含量;应用计算机图像分析技术测定气道壁厚度及血管密度。结果哮喘组的细胞总数和嗜酸性粒细胞高于对照组,多西环素组明显低于哮喘组,但仍高于对照组(均P<0.01);哮喘组大鼠肺组织和血清中MMP-9及VEGF的平均光密度值高于对照组,多西环素组明显低于哮喘组,但仍高于对照组(均P<0.01);哮喘组大鼠血清中的VEGF含量高于对照组,多西环素组低于哮喘组,但仍高于对照组(均P<0.01)。哮喘组大鼠的气道壁厚度与血管密度均高于对照组,多西环素组则明显低于哮喘组,但仍高于对照组(均P<0.01)。结论 MMP-9、VEGF对哮喘血管重塑有重要作用,多西环素具有减轻气道炎症和气道重塑的作用。Objective To study the effects of doxycycline on the expression of vascular endothelial growth factor（VEGF）,matrix metalloproteinases-9（MMP-9）,and asthma remodeling in asthmatic rats and to investigate the effects of doxycycline on asthma vascular remodeling.Methods Thirty-three male Sprague Dawley rats were randomly divided into three groups：control group,asthma group and doxycycline intervention group,11 rats a group.All rats were anesthetized by 1% pentobarbitalin and sampled.The numbers of total cells,neutrophils,lymphocytes and eosinophils in the bronchoalveolar lavage fluid were counted.Lung tissues were sliced and stained with HE.The expressions of VEGF and MMP-9 in lung tissues were observed by immunohistochemistry method,and mean optical densities of VEGF and MMP-9 were measured by image analysis software.ELISA was used to detect serum VEGF level.The airway wall thickness and vascular density were measured by image analysis software.Results Total number of cells and eosinophils in asthma group were higher than those of control group,and doxycycline intervention group were significantly lower than the asthma group,but still higher than the control group（all P〈0.01）.The MMP-9 and VEGF in the lung tissue of asthma group were significantly higher than those of control group,doxycycline intervention group were significantly lower than the asthma group,but still higher than control group（all P〈0.01）.The airway wall thickness and vascular density in asthma group were higher than those in control group,and doxycycline intervention group were significantly lower than the asthma group,but still higher than the control group（all P〈0.01）.Conclusion MMP-9 and VEGF showed important role in vascular remodeling of asthma,doxycycline can reduce airway inflammation and airway remodeling.

关 键 词：哮喘 血管内皮生长因子类 基质金属蛋白酶9 多西环素 

分 类 号：R562.25[医药卫生—呼吸系统]