阿胶对COPD模型小鼠的保护作用以及对MMP-2、MMP-9、TGF-β1水平的影响  

Protective Effect of Ejiao on COPD Model Mice and the Effect on MMP-2,MMP-9 and TGF-β1 Levels

作　　者：张喆 李娜 刘谦[1] 马云[1] 张玉[1] 兰红云[3] 姚成芳[3] Zhang Zhe;Li Na;Liu Qian;Ma Yun;Zhang Yu;Lan Hongyun;Yao Chengfang(Shandong University of Traditional Chinese Medicine, Jinan, 250014;Shandong University （Weihai）, Ocean College, Weihai, 264209;Institute of Basic Medicine, Shandong Academy of Medical Sciences, 250101)

机构地区：[1]山东中医药大学药学院,济南250014 [2]山东大学(威海)海洋学院,威海264209 [3]山东省医学科学院基础医学研究所,济南250101

出　　处：《基因组学与应用生物学》2018年第4期1813-1819,共7页Genomics and Applied Biology

基　　金：国家自然科学基金资助项目(81573728);山东省自然科学基金资助项目(ZR2015HM007);山东省医药卫生科技发展计划项目(2015WS0192)共同资助

摘　　要：利用香烟烟雾暴露法建立慢性阻塞性肺疾病（COPD）小鼠模型,观察阿胶对模型小鼠气道重塑及基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）、转化生长因子-β1（TGF-β1）因子表达的影响,初步探讨其治疗慢性阻塞性肺疾病的作用机制。将24只雄性C57BL/6小鼠随机分为3组,分别是对照组、模型组和阿胶组,模型组利用香烟烟雾暴露法建立COPD小鼠模型,阿胶组在模型组基础上每日按照3 g/kg体重给予0.2 m L阿胶烊化液灌胃。12周后采用ELISA法检测肺泡灌洗液中MMP-2、MMP-9、TGF-β1蛋白水平,利用RT-PCR法检测肺组织中MMP-2、MMP-9、TGF-β1 m RNA水平。结果表明,模型组小鼠气道壁和平滑肌明显增厚,气道管腔狭窄,黏膜下层稍变宽,有部分上皮细胞脱落,气道周围有炎性细胞浸润,肺间质明显增厚,阿胶组上述改变较模型组明显改善;模型组肺脏MMP-2、MMP-9、TGF-β1 m RNA水平和蛋白水平均显著升高（p〈0.01）,阿胶能显著降低肺泡灌洗液和肺脏组织中MMP-2、MMP-9、TGF-β1的表达水平（p〈0.01）。本研究表明香烟烟雾暴露会导致模型小鼠呼吸道和肺脏组织细胞外基质的降解和沉积失衡,造成气道重塑和肺实质破坏及间质增生,MMP-2、MMP-9、TGF-β1的异常表达在这一过程中发挥了重要作用,阿胶能通过调节MMP-2、MMP-9、TGF-β1的异常表达,有效抑制气道炎症和气道重塑的发生。Establishment of a chronic obstructive pulmonary disease（COPD） mouse model using cigarette smoke exposure to observe airway remodeling and matrix metalloproteinase-2（MMP-2）, matrix metalloproteinase-9（MMP-9） in model mice Effects of Transforming Growth Factor-β1（TGF-β1） Expression. The mechanism of chronic airway inflammation was explored. Twenty-four male C57 BL/6 mice were divided into 3 groups：control group, model group and gelatin group. Model group was established cigarette smoke exposure method to establish COPD mouse model, donkey-hide gelatin group was 3 g/kg daily on the basis of model group. The body weight was given 0.2 m L of Asarum gelatin solution. After 12 weeks, the levels of MMP-2, MMP-9 and TGF-β1 in bronchoalveolar lavage fluid were detected by ELISA. The levels of MMP-2, MMP-9 and TGF-β1 m RNA in lung tissue were detected by RT-PCR. The results showed that the airway walls and smooth muscles of mice in the model group were significantly thickened, the airway lumen was narrowed, the submucosa became slightly wider,some epithelial cells were detached, inflammatory cells infiltrated around the airways, and thickening of interstitial lungs. The above changes in the group were significantly improved compared with the model group; the MMP-2,MMP-9, and TGF-β1 factors transcription levels and protein levels in the lungs of the model group were significantly increased（p〈0.01）, and the gelatin could significantly reduce alveolar lavage fluid and lung tissue.The expression of the above factors（p〈0.01）. This study demonstrated that exposure to cigarette smoke leads to imbalance of degradation and deposition of extracellular matrix in the respiratory and lung tissues of model mice,resulting in airway remodeling and lung parenchymal destruction and interstitial hyperplasia, MMP-2, MMP-9,TGF-β1 Aberrant expression plays an important role in this process. Ejiao can effectively inhibit the occurrence of airway inflammation and airway remodeling by regulating the abnormal exp

关 键 词：阿胶 COPD模型 基质金属蛋白酶-2 基质金属蛋白酶-9 转化生长因子-Β1 

分 类 号：R285.5[医药卫生—中药学]