低氧性肺动脉高压大鼠肺内凝血酶敏感蛋白-1的表达

Expression of Thrombospondin-1 in the Lung of Hypoxic Pulmonary Hypertension 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)与肺血管重建的关系。方法将30只雄性Wistar大鼠分为正常对照组和低氧肺动脉高压组,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,采用免疫组化法检测各组大鼠肺内TSP-1和TGF-β1的表达,对肺组织切片进行图像分析。结果低氧3周后,低氧肺动脉高压组大鼠形成明显的肺动脉高压,管壁增厚和管腔狭窄,大鼠肺动脉压(2.86±0.39)kPa,右心室肥厚指数〔右心室(RV)/左心室+室间隔(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)kPa、(23.68±3.48)%、(23.63±9.74)%和(41.62±12.83)%〕相比升高(P<0.01);肺小动脉TSP-1免疫阳性染色灰度值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TGF-β1免疫阳性染色灰度值为1.38±0.05,与正常对照组(1.04±0.04)相比增强(P<0.01)。结论低氧所致TSP-1的合成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,其作用可能与活化TGF-β1有关。

Objective To investigate the expression of thrombospondin-1（TSP-1） in the lung of hypoxia-induced pulmonary hypertension rats.Methods Thirty male Wistar rats were divided into two groups,pulmonary hypertension group and control group.The mice in experimental group were exposed to isobaric hypoxia for 3 weeks,and those in control group were exposed to air.The pulmonary artery pressure was measured by right cardiac catheterization.The expression of TSP-1 and TGF-β1 in the lungs of rats were measured by immunohistochemical staining.The histological sections of the lungs were examined using a computerized image analyzer.Results After the induction of hypoxia for 3 weeks,the rats had pulmonary artery pressure increased with the thickening of the wall and the narrowing of the lumen of pulmonary arterioles.In the experimental group,the mean pulmonary artery pressure（mPAP） was（2.86±0.39） kPa,the index of right ventricular hypertrophy RV/（LV＋S） was（43.53±3.38）%,the ratio of vascular wall thickness/vascular external diameter（WA%） was（55.09±12.38）%,and the ratio of vascular wall area/total vascular area（WT%） was（35.24±11.2）%,which all were significantly increased in comparison with those of control group（mPAP（1.35±0.28） kPa,RV/（LV＋S）（23.68±3.48）%,WT%（23.63±9.74）%,WA%（41.62±12.83）%,respectively.P〈0.05）.The positive staining of TSP-1（1.32±0.04 vs.0.96±0.03） and TGF-β1（1.38±0.05 vs.1.04±0.04） in the wall of pulmonary arteriole of the rats exposed to hypoxia were significantly stronger than those of control rats（P〈0.01）.Conclusion The expression of TSP-1 appears to be increased in hypoxic pulmonary hypertension rats,which may contribute to the pathogenesis of hypoxic pulmonary vascular remodeling.