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首页> 外文OA文献 >Effects of macitentan and tadalafil monotherapy or their combination on the right ventricle and plasma metabolites in pulmonary hypertensive rats
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Effects of macitentan and tadalafil monotherapy or their combination on the right ventricle and plasma metabolites in pulmonary hypertensive rats

机译：Macitentan和Tadalafil Mootherapy的影响或它们在肺高血压大鼠右心室和血浆代谢物中的影响

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Pulmonary arterial hypertension is a severe respiratory disease characterized by pulmonary artery remodeling. RV dysfunction and dysregulated circulating metabolomics are associated with adverse outcomes in pulmonary arterial hypertension. We investigated effects of tadalafil and macitentan alone or in combination on the RV and plasma metabolomics in SuHx and PAB models. For SuHx model, rats were injected with SU5416 and exposed to hypoxia for three weeks and then were returned to normoxia and treated with either tadalafil (10 mg/kg in chow) or macitentan (10 mg/kg in chow) or their combination (both 10 mg/kg in chow) for two weeks. For PAB model, rats were subjected to either sham or PAB surgery for three weeks and treated with above-mentioned drugs from week 1 to week 3. Following terminal echocardiographic and hemodynamic measurements, tissue samples were collected for metabolomic, histological and gene expression analysis. Both SuHx and PAB rats developed RV remodeling/dysfunction with severe and mild plasma metabolomic alterations, respectively. In SuHx rats, tadalafil and macitentan alone or in combination improved RV remodeling/function with the effects of macitentan and combination therapy being superior to tadalafil. All therapies similarly attenuated SuHx-induced changes in plasma metabolomics. In PAB rats, only macitentan improved RV remodeling/function, while only tadalafil attenuated PAB-induced changes in plasma metabolomics.
机译：肺动脉高压是一种严重的呼吸系统疾病，其特征是肺动脉重塑。 RV功能障碍和失调的循环代谢物与肺动脉高压的不良结果有关。我们研究了塔达拉非（Tadalafil和Macitentan）的影响，或者组合在SUHX和PAB模型中的RV和血浆代谢组合。对于Suhx模型，大鼠用SU5416注射并暴露于缺氧三周，然后恢复到常规氧化，并用达拉多（10mg / kg）或Macitentan（10mg / kg中的10mg / kg）或它们的组合处理（10mg / kg）或它们的组合处理10毫克/千克的咸麻）两周。对于PAB模型，大鼠进行假或PAB手术三周，并从一周至第3周，用上述药物治疗3.在末端超声心动图和血液动力学测量后，收集组织样品进行代谢组，组织学和基因表达分析。 SUHX和PAB大鼠分别开发出RV重塑/功能障碍，分别具有严重和轻度血浆代谢物改变。在Suhx大鼠，单独或组合中的塔达拉非（Tadalafil和Macitentan），改善RV重塑/功能，具有Macitentan和组合治疗优于达拉非的影响。所有疗法同样衰减的SUHX诱导的血浆代谢组科的变化。在PAB大鼠中，只有Macitentan改善了RV重塑/功能，而只有Tadalafil衰减的PAB诱导的血浆代谢组学变化。

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