游泳运动对低氧性肺动脉高压大鼠肺组织apelin及其受体表达的影响

Effect of swimming exercise on the expression of apelin and its receptor in pulmonary tissues of rats with hypoxic pulmonary hypertension

目的:探讨游泳运动对大鼠肺组织新的小分子活性肽apelin及其受体(APJ)表达的影响。方法:45只雄性大鼠随机分成三组:正常对照组、低氧组(七周)和游泳组(低氧+游泳锻炼七周组,低氧3周后,于每天入低氧舱前行无负重游泳运动60 min,每天1次)。七周后测定各组大鼠平均肺动脉压(mPAP)、右心室与左心室加室间隔的重量比[RV/(LV+S)]、肺细小动脉管壁面积/管总面积(WA/TA)、管腔面积/管总面积(CA/TA)及中膜厚度(PAMT)。免疫蛋白印迹与免疫组化法测定肺组织apelin/APJ的蛋白表达。结果:①低氧组mPAP和RV/(LV+S)比正常对照组分别高73.6%和31.2%(P均<0.01),而游泳组比低氧组分别低21.1%和8.9%(P均<0.05)。②低氧组WA/TA和PAMT较正常对照组分别高70.8%和102%,而游泳组较低氧组分别低24.8%和40.1%(P均<0.01)。低氧组CA/TA较正常对照组低15.1%,而游泳组较低氧组高10.3%(P均<0.01)。③低氧组肺组织apelin蛋白表达较正常对照组上调374%(P<0.01),而APJ蛋白表达下调87.1%(P均<0.01);游泳组肺组织apelin蛋白表达较低氧组下调48%,而APJ蛋白表达上调287%(P均<0.01)。④apelin蛋白主要在血管外膜及炎症细胞胞浆内表达,APJ蛋白主要在血管内膜、外膜及炎症细胞上表达。结论:游泳运动减缓肺动脉高压和肺血管重塑作用可能与调节肺组织apelin/APJ系统的表达有关。

Objective： To study the effects of swimming exercise on the expression of apelin and its receptor（APJ） system in pulmonary tissues of rats with pulmonary hypertension induced by hypoxia.Methods： Forty-five male SD rats were randomly divided into control group,hypoxia group（seven-week） and swimming group（four-week swimming group after three-week hypoxia）.The animal model of hypoxic pulmonary hypertension was established by exposing the rats to isobaric hypoxic chamber（8 h/d,6 d/w）.The rats of swimming group swam 60 min/ day,7 d/week for 4 weeks after three-week hypoxia.The mean pulmonary arterial pressure（mPAP） and the mean carotid arterial pressure（mCAP） were measured by either right or left cardiac catheterization,and the weight ratio of right ventricule/left ventricle plus septum were calculated.The Masson＇s trichrome stained lung specimens were used by light microscope to examine the vessel wall area/total area（WA/TA）,vessel cavity area/total area（CA/TA） and media thickness of pulmonary arterioles（PAMT）.Meanwhile,apelin/APJ expressions were determined by Western blot and immunohistochemistry.Results： ①mPAP and RV/（LV＋S） of hypoxia group were higher than those of control group by 73.6% and 31.2%（P0.01）,and mPAP and RV/（LV＋S） of swimming group were lower than those of hypoxia group by 21.1%and 8.9 %（P0.05）,respectively.②Masson＇s trichrome staining revealed that WA/TA and PAMT of hypoxia group were higher than those of control group by 70.8% and 102%.However,WA/TA and PAMT of swimming group were lower than those of hypoxia group by 24.8% and 40.1%（all P0.01）,respectively.CA/TA of hypoxia group was lower than that of control group by 15.1%,and CA/TA of swimming group was lower than that of hypoxia group by 10.3%（all P0.01）.③Compared with control group,hypoxia group showed up-regulated apelin expression and down-regulated APJ expression in pulmonary tissues（all P0.01）.Compared with hypoxia group,swimming group showed decreased apelin expression and elevated APJ expression in pulmonary tissues（all P0.01）.④Apelin localized mainly in intracytoplasm of inflammatory cell and tunica adventitia of vessel,and APJ were in vascular intima and tunica externa and plasmalemma of inflammatory cell.Conclusion： The improving effect of swimming exercise on hypoxic pulmonary hypertension in rats could be mediated by regulating the pulmonary apelin/APJ system.