梅拉通宁对肺动脉高压大鼠右静脉氧化压力和 TLR4/NF-kβ 炎症途径的影响。

IF 3.8 3区 医学 Q2 CELL BIOLOGY Molecular and Cellular Endocrinology Pub Date : 2024-07-11 DOI:10.1016/j.mce.2024.112330
Cristiane Dias Lisboa , José Luciano Maciel de Souza , Custódio José Gaspar, Patrick Turck, Vanessa Duarte Ortiz, Isabel Cristina Teixeira Proença, Tânia Regina G. Fernandes, Elissa Fernandes, Silvio Tasca, Cristina Campos Carraro, Adriane Belló-Klein, Alex Sander da Rosa Araujo, Alexandre Luz de Castro
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引用次数: 0

摘要

肺动脉高压(PAH)的特点是平均肺动脉压升高和右心室(RV)受损,并发展为心力衰竭和过早死亡。有研究评估了褪黑激素作为一种有前景的 PAH 治疗策略的作用。本研究旨在评估褪黑激素对 PAH 大鼠 RV 中氧化应激和 TLR4/NF-kβ 炎症通路的影响。雄性 Wistar 大鼠被分为以下几组:对照组、单氯他林组(MCT)和单氯他林加褪黑素组。最后两组在实验方案的第一天腹腔注射一次 MCT(60 毫克/千克)。单克洛塔林加褪黑素组在 21 天内每天灌胃 10 毫克/千克褪黑素。进行超声心动图分析,并收集 RV 进行形态分析、氧化应激和分子评估。本研究的主要发现是,通过 TAPSE 评估,服用褪黑素可减轻一缩醛引起的 RV 功能下降。此外,褪黑素还能防止 PAH 导致的 RV 舒张面积缩小。此外,接受褪黑激素治疗的动物并没有表现出 ROS 水平或 NF-kβ 表达的增加。此外,与对照组和单克洛塔林组相比,单克洛塔林加褪黑素组的TLR4表达减少。据我们所知,这是第一项证明褪黑激素对 PAH 大鼠 RV 中 TLR4/NF-kβ 通路有积极影响的研究。从这个意义上说,这项研究使我们有可能将褪黑激素视为减轻 PAH 引起的 RV 改变的可能盟友。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Melatonin effects on oxidative stress and on TLR4/NF-kβ inflammatory pathway in the right ventricle of rats with pulmonary arterial hypertension

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.

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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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