Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600, Santa Cecília, CEP: 90035-003, Porto Alegre, RS, Brazil.
Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Ramiro Barcelos Street, 2600, Santa Cecília, CEP: 90035-003, Porto Alegre, RS, Brazil.
Mol Cell Endocrinol. 2024 Oct 1;592:112330. doi: 10.1016/j.mce.2024.112330. Epub 2024 Jul 11.
Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure and a compromised the right ventricle (RV), together with progression to heart failure and premature death. Studies have evaluated the role of melatonin as a promising therapeutic strategy for PAH. The objective of this study was to evaluate melatonin's effects on oxidative stress and on the TLR4/NF-kβ inflammatory pathway in the RV of rats with PAH. Male Wistar rats were divided into the following groups: control, monocrotaline (MCT), and monocrotaline plus melatonin groups. These two last groups received one intraperitoneal injection of MCT (60 mg/kg) on the first day of experimental protocol. The monocrotaline plus melatonin group received 10 mg/kg/day of melatonin by gavage for 21 days. Echocardiographic analysis was performed, and the RV was collected for morphometric analysis oxidative stress and molecular evaluations. The main findings of the present study were that melatonin administration attenuated the reduction in RV function that was induced by monocrotaline, as assessed by TAPSE. In addition, melatonin prevented RV diastolic area reduction caused by PAH. Furthermore, animals treated with melatonin did not show an increase in ROS levels or in NF-kβ expression. In addition, the monocrotaline plus melatonin group showed a reduction in TLR4 expression when compared with control and monocrotaline groups. To our knowledge, this is the first study demonstrating a positive effect of melatonin on the TLR4/NF-kβ pathway in the RV of rats with PAH. In this sense, this study makes it possible to think of melatonin as a possible ally in mitigating RV alterations caused by PAH.
肺动脉高压（PAH）的特征是平均肺动脉压升高和右心室（RV）功能受损，同时伴有心力衰竭和过早死亡。研究已经评估了褪黑素作为 PAH 有前途的治疗策略的作用。本研究的目的是评估褪黑素对 PAH 大鼠 RV 氧化应激和 TLR4/NF-kβ炎症途径的影响。雄性 Wistar 大鼠分为以下几组：对照组、野百合碱（MCT）组和野百合碱加褪黑素组。后两组在实验方案的第一天接受一次腹腔注射 MCT（60mg/kg）。褪黑素加褪黑素组通过灌胃给予 10mg/kg/天的褪黑素 21 天。进行超声心动图分析，并收集 RV 进行形态计量学分析、氧化应激和分子评估。本研究的主要发现是褪黑素给药减轻了野百合碱诱导的 RV 功能下降，如 TAPSE 评估所示。此外，褪黑素预防了 PAH 引起的 RV 舒张面积减少。此外，用褪黑素治疗的动物没有表现出 ROS 水平或 NF-kβ表达增加。此外，与对照组和野百合碱组相比，野百合碱加褪黑素组 TLR4 表达减少。据我们所知，这是第一项证明褪黑素对 PAH 大鼠 RV 中 TLR4/NF-kβ 途径具有积极影响的研究。在这方面，这项研究使人们有可能认为褪黑素是减轻 PAH 引起的 RV 改变的一种可能的盟友。
