基质金属蛋白酶在慢性低氧高二氧化碳大鼠肺血管重建中的作用

Role of matrix metalloproteinases in pulmonary vascular remodeling in rats with pulmonary hypertension induced by chronic hypoxia hypercapnia

目的 :研究基质金属蛋白酶在低氧高二氧化碳大鼠肺血管重建中的作用。方法 :将SD大鼠分为正常对照组 (C组 ) ,3w低氧高二氧化碳组 (H组 )。采用光镜、图像分析、免疫杂交等方法 ,观察各组大鼠肺动脉平均压 (mPAP)、颈动脉平均压 (mCAP)、右心室 / (左心室 +室间隔 )重量比RV/ (LV +S)、肺细小动脉显微结构、肺组织羟脯氨酸含量及明胶酶A、B(MMP 2、MMP 9)的表达变化。结果 :①H组mPAP、RV/LV +S显著高于C组 (P <0 .0 1)。②肺组织匀浆羟脯氨酸含量H组显著高于C组 (P <0 .0 1)。③光镜下肺细小动脉管壁面积 /管总面积 (WA/TA)、管腔面积 /管总面积 (EA/TA)、肺细小动脉中膜厚度 (PAMT)C组明显低于H组 (P <0 .0 1)。④免疫杂交法检查发现肺组织匀浆MMP 2、MMP 9含量H组较C组显著升高 (P <0 .0 1)。结论 :低氧高二氧化碳促使基质金属蛋白酶表达升高 。

Objective:To investigate the role of matrix metalloproteinases in pulmonary vascular remodeling in rats with chronic hypoxia and hypercapnia induced pulmonary hypertension.Methods:Twenty male Sprague Dawley rats were randomly divided into two groups:normal control group(C),hypoxia hypercapnia group(H). Content of matrix metalloproteinases was measured with enzyme combinate immune cross methods.Results:①The mean pulmonary artery pressure(mPAP) and weight ratio of right ventricle to left ventricle and septum(RV/LV+S) of H group were higher than C group(P<0.01).②Content of hydroxyproline in H group was significantly higher than that in C group(P<0.01).③Light microscopy showed that vessel wall area/total area(WA/TA),vessel cavity area/total area(EA/TA) and media thickness of pulmonary arterioles were much higher in rats of H group than those in C group(P<0.01).④The observation under electron microscopy showed proliferation of smooth muscle cells in media and deposition of collagen in pulmpnary arterioles in rats of H group,but no same performance was found in C group.⑤Pulmonary tissue homogenates MMP 2 and MMP 9 levels of H group were significantly increased(P<0.01),compared with control group.Conclusion:Expression of matrix metalloproteinases in pulmonary tissues was enhanced by hypoxia hypercapnia,which could be involved in pulmonary vascular remodeling in the rats with pulmonary hypertension.