Different patterns of pulmonary vascular disease induced by type 1 diabetes and moderate hypoxia in rats
Different patterns of pulmonary vascular disease induced by type 1 diabetes and moderate hypoxia in rats
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DOI：
10.1113/expphysiol.2011.062257
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发表时间：
2012-05-01
影响因子：
2.7
通讯作者：
Moreno, Laura
中科院分区：
文献类型：
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作者：
Moral-Sanz, Javier;Lopez-Lopez, Jose G.;Moreno, Laura
虽然1型和2型糖尿病与全身心血管疾病的发病率密切相关，但在最近的流行病学数据显示糖尿病可能是肺动脉高压的危险因素之前，与肺血管疾病的关系几乎被忽视。最近的实验研究表明，糖尿病引起的肺功能改变不足以升高肺动脉压。本研究的目的是评估糖尿病对肺动脉高压其他危险因素敏感性的影响。因此，我们分析了糖尿病合并中度缺氧对肺动脉高压的经典标记物的影响。对照组(生理盐水组)和糖尿病(链脲佐菌素70 mg·kg~(-1)组)雄性Wistar京都大鼠连续4周，暴露于常氧或中度常压低氧(14%)中2周。低氧，而不是糖尿病，强烈降低电压门控性钾电流，而糖尿病，而不是低氧，导致肺动脉内皮功能障碍。两种因素单独诱导肺血管重塑，下调肺组织骨形态发生蛋白受体2的表达。糖尿病而不是低氧可诱导肺巨噬细胞的浸润，两者联合作用时巨噬细胞的浸润明显增加。糖尿病加低氧导致了舒张压和平均肺动脉压以及右心室重量的适度增加，而单独使用这两个因素并没有显著影响。中度缺氧组和糖尿病组肺动脉高压标志物的变化模式不同，除巨噬细胞聚集外，无协同作用，两者联合作用才能引起中度的肺动脉压升高。
Although type 1 and type 2 diabetes are strongly associated with systemic cardiovascular morbidity, the relationship with pulmonary vascular disease had been almost disregarded until recent epidemiological data revealed that diabetes might be a risk factor for pulmonary hypertension. Recent experimental studies suggest that diabetes induces changes in lung function insufficient to elevate pulmonary pressure. The aim of this study was to assess the effects of diabetes on the sensitivity to other risk factors for pulmonary hypertension. We therefore analysed the effects of the combination of diabetes with exposure to moderate hypoxia on classical markers of pulmonary hypertension. Control (saline-treated) and diabetic (70 mg kg-1 streptozotocin-treated) male WistarKyoto rats were followed for 4 weeks and exposed to normoxia or moderate normobaric hypoxia (14%) for another 2 weeks. Hypoxia, but not diabetes, strongly reduced voltage-gated potassium currents, whereas diabetes, but not hypoxia, induced pulmonary artery endothelial dysfunction. Both factors independently induced pulmonary vascular remodelling and downregulated the lung bone morphogenetic protein receptor type 2. However, diabetes, but not hypoxia, induced pulmonary infiltration of macrophages, which was markedly increased when both factors were combined. Diabetes plus hypoxia induced a modest increase in diastolic and mean pulmonary artery pressure and right ventricular weight, while each of the two factors alone had no significant effect. The pattern of changes in markers of pulmonary hypertension was different for moderate hypoxia and diabetes, with no synergic effect except for macrophage recruitment, and the combination of both factors was required to induce a moderate elevation in pulmonary arterial pressure.