氯沙坦对大鼠慢性阻塞性肺疾病模型气道细胞外基质重塑的作用

Effects of Losartan on Remodeling of Airway Extracellular Matrix in Rat Models with Chronic Obstructive Pulmonary Disease

目的研究氯沙坦对大鼠慢性阻塞性肺疾病(COPD)模型细胞外基质重塑的干预作用,并探讨其机制。方法SD大鼠30只,随机分为对照组、模型组、氯沙坦组,各10只。采用熏香烟加气管内滴入脂多糖法建立COPD模型,以HE切片及大鼠动脉血气分析评价COPD大鼠模型形态和功能改变。双抗夹心酶联免疫吸附法(ELISA法)测定支气管肺泡灌洗液(BALF)中基质金属蛋白酶-9(MMP-9)、组织抑制因子-1(TIMP-1)的含量,用免疫组化法检测MMP-9、TIMP-1的表达。结果模型组支气管肺组织中MMP-9、TIMP-1表达情况〔分别为:(27.2±1.6)、(24.7±1.8)〕与对照组〔(12.0±1.3)、(12.0±1.3)〕比较差异均有统计学意义(P<0.01)。治疗组MMP-9、TIMP-1表达情况〔分别为:(17.0±1.5)、(15.0±1.7)〕与对照组比较差异均有统计学意义(P<0.05),与模型组比较差异亦均有统计学意义(P<0.01)。模型组BALF中MMP-9、TIMP-1含量〔分别为:(133.0±7.0)μg/L、(77.6±5.1)μg/L〕及MMP-9/TIMP-1的比值(1.7±1.6)与对照组比较差异均有统计学意义(P<0.01);治疗组MMP-9、TIMP-1的含量〔分别为:(42.9±3.7)μg/L、(37.8±2.8)μg/L〕及MMP-9/TIMP-1的比值(1.1±0.1)与模型组比较差异均有统计学意义(P<0.05)。结论MMP-9、TIMP-1与COPD细胞外基质重塑有关,氯沙坦能防治COPD细胞外基质重塑,这一效应与其恢复MMP-9/TIMP-1的平衡有关。

Objectives To investigate the intervention effect of Losartan on remodeling of extracellular matrix in rat models with chronic obstructive pulmonary disease(COPD).Methods Thirty SD rats were randomized into groups of control,model and Losartan,10 in each.COPD models were established by tobacco fumigating in combination of intratracheal instillation of lipopolysaccharide.The changes of morphous and function of COPD models were evaluated by HE slices and arterial blood gas analysis,the levels of matrix metall...