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白藜芦醇可预防野百合碱诱导的肺动脉高压引起的右心室重构和功能障碍,但对肺血管的改善作用有限。

Resveratrol Prevents Right Ventricle Remodeling and Dysfunction in Monocrotaline-Induced Pulmonary Arterial Hypertension with a Limited Improvement in the Lung Vasculature.

机构信息

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ave. Morones Prieto 3000, 64710 Monterrey, N.L., Mexico.

Centro de Investigación Biomédica, Hospital Zambrano-Hellion, Tec Salud, Tecnologico de Monterrey, Batallón San Patricio 112 Col. Real de San Agustín, 66278 San Pedro Garza García, N.L., Mexico.

出版信息

Oxid Med Cell Longev. 2020 Feb 3;2020:1841527. doi: 10.1155/2020/1841527. eCollection 2020.

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening disease that is characterized by an increase in pulmonary vascular pressure, leading to ventricular failure and high morbidity and mortality. Resveratrol, a phenolic compound and a sirtuin 1 pathway activator, has known dietary benefits and is used as a treatment for anti-inflammatory and cardiovascular diseases. Its therapeutic effects have been published in the scientific literature; however, its benefits in PAH are yet to be precisely elucidated. Using a murine model of PAH induced by monocrotaline, the macroscopic and microscopic effects of a daily oral dose of resveratrol in rats with PAH were evaluated by determining its impact on the lungs and the right and left ventricular function. While most literature has focused on smooth muscle cell mechanisms and lung pathology, our results highlight the relevance of therapy-mediated improvement of right ventricle and isolated cardiomyocyte physiology in both ventricles. Although significant differences in the pulmonary architecture were not identified either micro- or macroscopically, the effects of resveratrol on right ventricular function and remodeling were observed to be beneficial. The values for the volume, diameter, and contractility of the right ventricular cardiomyocytes returned to those of the control group, suggesting that resveratrol has a protective effect against ventricular dysfunction and pathological remodeling changes in PAH. The effect of resveratrol in the right ventricle delayed the progression of findings associated with right heart failure and had a limited positive effect on the architecture of the lungs. The use of resveratrol could be considered a future potential adjunct therapy, especially when the challenges to making a diagnosis and the current therapy limitations for PAH are taken into consideration.

摘要

肺动脉高压(PAH)是一种危及生命的疾病,其特征是肺血管压力增加,导致心室衰竭和高发病率和死亡率。白藜芦醇是一种酚类化合物和 SIRT1 途径激活剂,具有已知的饮食益处,被用作抗炎和心血管疾病的治疗方法。其治疗效果已在科学文献中公布;然而,其在 PAH 中的益处尚未得到精确阐明。本研究使用野百合碱诱导的 PAH 小鼠模型,通过确定其对肺和右、左心室功能的影响,评估白藜芦醇在 PAH 大鼠中的每日口服剂量的宏观和微观作用。虽然大多数文献都集中在平滑肌细胞机制和肺病理学上,但我们的结果强调了治疗介导的右心室和分离的心肌细胞生理学改善在两个心室中的相关性。虽然在微观或宏观上都没有发现肺结构的显著差异,但观察到白藜芦醇对右心室功能和重塑的有益作用。右心室心肌细胞的体积、直径和收缩力值恢复到对照组的水平,表明白藜芦醇对心室功能障碍和 PAH 病理性重塑变化具有保护作用。白藜芦醇在右心室的作用延缓了与右心衰竭相关的发现的进展,并对肺的结构有有限的积极影响。考虑到 PAH 的诊断挑战和当前治疗的局限性,白藜芦醇的使用可以被认为是一种未来的潜在辅助治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfb2/7023844/99e0e0153f0f/OMCL2020-1841527.001.jpg

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