UMRS 999, INSERM et Univ, Paris-Sud, Laboratoire d'Excellence (LabEx) en Recherche sur le Médicament et l'Innovation Thérapeutique (LERMIT), Centre Chirurgical Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis Robinson, France.
Respir Res. 2014 Jun 14;15(1):65. doi: 10.1186/1465-9921-15-65.
The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function.
Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14-28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis.
The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001).
Through its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.
肺动脉高压（PAH）患者的预后主要取决于右心室对肺血管阻力增高导致的后负荷增加的反应。然而，目前对于 PAH 治疗药物对心脏的影响知之甚少。最近，炎症被认为与 PAH 的病理生理学有关。N-乙酰半胱氨酸（NAC）是一种众所周知的安全抗氧化药物，具有免疫调节和心脏保护作用。因此，我们假设 NAC 可以通过降低炎症反应、保护肺血管系统和右心功能，减轻暴露于单环酸（MCT）的大鼠的肺动脉高压（PH）严重程度。
在 MCT 暴露后第 14-28 天，用生理盐水处理的对照组、MCT 暴露组、MCT 暴露并用 NAC 处理组的大鼠，通过血流动力学参数（右心室收缩压、平均肺动脉压和心输出量）、右心室肥厚、肺血管形态计量学、肺炎症细胞免疫组化（单核细胞/巨噬细胞和树突状细胞）、IL-6 表达、心肌细胞肥大和心脏纤维化，评估 MCT 暴露第 28 天的大鼠。
NAC 治疗显著降低了肺血管重塑、肺炎症，并改善了总肺阻力（从 MCT 组的 0.71±0.05 降低到 MCT+NAC 组的 0.50±0.06，p<0.05）。NAC 治疗还改善了右心室功能，同时显著降低了心肌细胞肥大（MCT 和 MCT+NAC 组分别为 625±69μm2和 439±21μm2，p<0.001）和心脏纤维化（MCT 和 MCT+NAC 组分别为 14.1±0.8%和 8.8±0.1%，p<0.001）。
通过其免疫调节和心脏保护作用，NAC 对实验性 PH 中的肺血管和右心功能具有有益的作用。
