低氧大鼠肺内凝血酶敏感蛋白-1与表皮生长因子受体表达的变化

The Expression of Thrombospondin-1 and Epidermal Growth Factor Receptor in Lungs of Hypoxic Rats

目的:了解低氧肺动脉高压时肺内凝血酶敏感蛋白-1(TSP-1)和表皮生长因子受体(EGFR)表达与肺血管重建的关系。方法:将20只雄性Wistar大鼠分为低氧性肺动脉高压组(低氧组)和对照组各10只,低氧组以常压低氧3周建立肺动脉高压模型,以微导管法测定2组大鼠肺动脉压,采用免疫组化和原位杂交法检测大鼠肺内TSP-1、EGFR蛋白及mRNA的表达,对肺组织切片进行图像分析。结果:低氧3周后,低氧组形成明显的肺动脉高压模型,肺小动脉管壁增厚和管腔狭窄,低氧组肺动脉压、右心室肥厚指数[RV/(LV+S)]、管壁厚度占外径的百分比(WT%)、管壁面积占血管总面积的百分比(WA%)均较对照组明显升高(P<0.05);低氧组肺小动脉TSP-1、EGFR蛋白阳性染色和TSP-1、EGFR mRNA阳性染色均较对照组明显增强(P<0.01)。结论:低氧所致TSP-1及EGFR增多在低氧性肺血管重建和肺动脉高压的发病过程中起一定的作用。

Objective： To test the role of thrnmbospondin-1 （TSP-1） and epidermal growth factor receptor （EGFR） in the development of hypoxie pulmonary hypertension. Methods： Twenty male Wistar rats were divided into two groups, control group and hypoxia group. Rats were exposed to air and isobaric hypoxia for 3 weeks to establish models for pulmonary hypertension. The pulmonary artery pressure was measured by right cardiac catheterization in two groups. The expressions of TSP-1 and EGFR protein in the lungs of rats were measured by immunohistochemical staining and in situ hybridization. The lung histological sections were examined using a computerized image analyzer. Results： The pulmonary artery pressure of rats increased in hypoxia group, The chronic hypoxia elicited the thickening of the wall and the narrowing of the lumen of pulmonary arterioles. The pulmonary artery pressure, the index of right ventrieular hypertrophy （RW（LV＋S））, the ratio of vascular wall thickness/vascular external diameter （WA%） and the ratio of vascular wall area/total vascular area （WT%） were significantly higher in hypoxia group compared to those of control group （P 〈 0.05）. The positive staining of TSP-1, EGFR, TSP-1 mRNA and EGFR mRNA were significantly stronger in the wall of pulmonary arteriole of hypoxia group than those of control group （P 〈 0.01）. Conclusion： The TSP-1 and EGFR may play an important role in the pathogenesis process of hypoxic pulmonary vascular remodeling and pulmonary hypertension.