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首页> 外文期刊>Cellular Physiology and Biochemistry >Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway
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Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway

机译:糖皮质激素的过量通过激活血管紧张素II途径诱导心脏功能障碍

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Background: Glucocorticoid is widely used as an anti-inflammatory drug in various diseases however excess of it often causes cardiovascular complications. The present study was undertaken to understand the molecular mechanism of glucocorticoid-induced cardiac dysfunction. Methods: Rats were treated daily with synthetic glucocorticoid, dexamethasone with or without mifepristone or losartan up to 15 days. Hemodynamic parameters were measured by PV-loop method using Millar's instrument. Cardiac remodelling, fibrosis and oxidative stress were monitored after 15 days. Results: The systolic blood pressure was increased whereas the heart beat and cardiac output (n=6) were decreased by dexamethasone. Dexamethasone caused increase in the heart weight to body weight ratio (P<0.001, n=20), increased level of mRNA of atrial natriuretic peptide and an increased deposition of collagens in the extracellular matrix of the left ventricle which were inhibited by both mifepristone and losartan. The rate of oxygen consumption was decreased in association with increased levels of hypoxia inducible factor 1 lipid peroxidation (P<0.01, n=3) and superoxide dismutase activity (P<0.01, n=3) in dexamethasone treated rat heart. All these changes were reversed by mifepristone and losartan. Conclusions: The excess of glucocorticoid induces cardiac remodelling and pathophysiolgical changes of the myocardium via angiotensin II signalling pathway. Copyright
机译:背景:糖皮质激素被广泛用作各种疾病的抗炎药,但是过量使用糖皮质激素通常会导致心血管并发症。进行本研究以了解糖皮质激素诱导的心脏功能障碍的分子机制。方法:每天用合成的糖皮质激素,地塞米松(含或不含米非司酮或氯沙坦)治疗大鼠长达15天。血流动力学参数是使用Millar仪器通过PV回路法测量的。 15天后监测心脏重塑,纤维化和氧化应激。结果:地塞米松使收缩压升高,而心跳和心输出量降低(n = 6)。地塞米松引起心脏重量与体重比的增加(P <0.001,n = 20),心钠素的mRNA水平增加以及左心室细胞外基质中胶原蛋白的沉积增加,米非司酮和米非司酮均抑制氯沙坦。与地塞米松治疗的大鼠心脏缺氧诱导因子1脂质过氧化水平升高(P <0.01,n = 3)和超氧化物歧化酶活性(P <0.01,n = 3)相关,氧气消耗率降低。所有这些变化均被米非司酮和氯沙坦逆转。结论:糖皮质激素的过量通过血管紧张素II信号通路诱导心肌重构和心肌的病理生理变化。版权

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