【摘要】 目的 探讨凝血酶敏感蛋白-1（TSP-1）在低氧性肺动脉高压发病机制中的可能作用。 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平均肺动脉高压模型，以微导管法测定两组大鼠平均肺动脉压力（mPAP），采用图像分析测量肺小动脉管壁厚度，计算管壁厚度占血管外径的百分比（WT%）和管壁面积占血管总面积的百分比（WA%），酶联免疫吸附法检测大鼠血清TSP-1的浓度和荧光定量PCR法观察大鼠肺组织TSP-1 mRNA的表达。 结果 低氧3周后，低氧组大鼠mPAP为（2.86±0.39）kPa，右心室肥厚指数〔右心室/(左心室+室间隔)〕为(43.53±3.38)%、WT%为(35.24±11.20)%，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，差异具有统计学意义（P<0.01）；血清TSP-1浓度高于对照组〔(758.6±46.4) ng/mL vs. (382.7±32.8) ng/mL，P<0.05〕，大鼠肺组织TSP-1 mRNA的含量亦较对照组增加〔(6.53±2.43) vs. (3.07±1.87)，P<0.01〕。相关分析表明，TSP-1 mRNA与WT%、WA%、mPAP呈正相关（r=0.748， 0.686，0.942，P<0.05）。 结论 低氧后大鼠肺组织TSP-1的合成和释放增多，TSP-1增加可能与低氧性肺动脉高压的发生有关。
英文摘要:
【Abstract】 Objective To investigate the expression of thrombospondin-1 (TSP-1) in serum and pulmonary arterioles of rats with 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 mean pulmonary artery pressure (mPAP) was measured by right cardiac catheterization. The rates of wall thickness/external diameter (WT%) and wall area/total vascular area (WA%) were calculated. The TSP-1 level in serum was measured by enzyme-linked immunosorbent assay. TSP-1 mRNA expression in lung tissue was evaluated by quantitative PCR. Results The pulmonary artery pressure increased in the hypoxia exposed rats. 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 pulmonary artery pressure, the index of right ventricular hypertrophy 〔RV/(LV+S)〕, WA% and WT% compared to the controls 〔mPAP:(2.86±0.39) kPa vs. (1.35±0.28) kPa; RV/(LV+S): (43.53±3.38)% vs. (23.68±3.48)%; WT%: (35.24±11.20)% vs. (23.63±9.74)%; WA%: (55.09±12.38)% vs. (41.62±12.83)% respectively, P<0.05〕. In hypoxic group, the expression of TSP-1 mRNA in the lung was significantly up-regulated, the expression level of TSP-1 in serum was higher than that in control group （P<0.01）. Linear correlation analysis showed that TSP-1 mRNA was positively associated with WT%,WA% and mPAP （r=0.748， 0.686，0.942 respectively, P<0.05）. Conclusion The TSP-1 may play an important role in the pathogenesis process of hypoxic pulmonary vascular remodeling and pulmonary hypertension.
