低氧大鼠肺内TSP-1与EGFR的表达变化及意义

摘要 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（n=10）和对照组（n=10）两组，肺动脉高压组以常压低氧建立大鼠肺动脉高压模型，以微导管法测定各组大鼠肺动脉压，采用免疫组化和原位杂交法检测各组大鼠肺内TSP-1蛋白、EGFR蛋白及TSP-1mRNA、EGFRmRNA的表达，对肺组织切片进行图象分析。 结果 低氧3周后，低氧组大鼠形成明显的肺动脉高压，管壁增厚和管腔狭窄，低氧组大鼠肺动脉压（2.86±0.39）kP，右心室肥厚指数﹝RV/(LV+S)﹞为43.53±3.38、管壁厚度占外径的百分比（WT%）为35.24±11.2，管壁面积占血管总面积的百分比（WA％）为55.09±12.38，分别与正常对照组(1.35±0.28)kP、23.68±3.48、23.63±9.74和41.62±12.83相比明显升高（P<0.01）；肺小动脉TSP-1免疫阳性染色在低氧肺动脉高压组大鼠为1.32±0.04，与正常对照组（0.96±0.03）相比增强（P<0.01），低氧肺动脉高压组大鼠EGFR蛋白免疫染色为1.48±0.07，与正常对照组（1.09±0.02）相比增强（P<0.01）。肺小动脉TSP-1mRNA阳性染色在低氧组大鼠为1.44±0.03，与正常对照组1.12±0.05相比明显增强（P<0.01），低氧组大鼠EGFRmRNA阳性染色为1.43±0.05，与正常对照组1.10±0.04相比明显增强（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。

The Expression of Thrombospondin-1 and Epidermal Growth Factor Receptor in the Lung of Rats Exposed to Hypoxia

Abstract Objective To test the role of thrombospondin-1(TSP-1) and epidermal growth factor receptor (EGFR) in the development of hypoxic pulmonary hypertension. Methods Twenty male Wistar rats were divided into two groups and exposed to air and isobaric hypoxia for 3 weeks, respectively. The pulmonary artery pressure was measured by right cardiac catheterization. The expression of TSP-1 and EGFR in the lungs of rats were measured by immunohistochemical staining and in situ hybridization. The histological sections of the lungs were examined using a computerized image analyzer. Results The pulmonary artery pressure in the exposed rats increased. The chronic hypoxia also elicited the thicking of the wall and the narrowing of the lumen of pulmonary arterioles. It led to the increases of the pulmonary artery pressure 、the index of righr ventricular hypertrophy ﹝RV/(LV+S)﹞、 the ratio of vascular wall thickness/vascular external diameter(WA%) and the ratio of vascular wall area/total vascular area(WT%) compared to the controls (PAP2.86±0.39kP vs 1.35±0.28kP;﹝RV/(LV+S): 43.53±3.38 vs 23.68±3.48; WT%:35.24±11.2 vs 23.63±9.74; WA%:55.09±12.38 vs 41.62±12.83 respectively, p<0.05). The positive staining of TSP-1 protein and TSP-1mRNA in the wall of pulmonary arteriole of the exposed rats were significantly stronger than those of controls （P<0.01）, so as that of EGFR. Conclusions The TSP-1 and EGFR may play an important role in the pathogenesis process of hypoxic pulmonary vascular remodeling and pulmonary hypertension.