PM2.5诱发慢性阻塞性肺病的体内和体外模型:关注RTA-408的作用。

IF 2.7 3区 医学 Q2 RESPIRATORY SYSTEM
Yibing Niu, Ling Zhang, Sumin Guo, Shucai Wu
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引用次数: 0

摘要

导言:炎症和氧化应激是慢性阻塞性肺病(COPD)发病机制中的重要因素。目前治疗慢性阻塞性肺病的方法主要是改善炎症引起的症状,而不是治愈疾病,因此,关注上游途径的新兴研究可能有助于开发有效的治疗方法。流行病学调查显示,暴露于细颗粒物(PM2.5)可通过核因子NF-E2-相关因子(Nrf2)途径引起肺部炎症和氧化应激,从而导致慢性阻塞性肺病。Nrf2是调节抗炎和抗氧化应激的重要转录因子,其表达水平异常或转录活性改变与慢性阻塞性肺病的发生和发展有关。目的:本研究利用PM2.5在体外建立HBE细胞模型,在体内建立大鼠模型模拟慢性阻塞性肺疾病,研究Nrf2激活剂RTA-408对PM2.5诱导的慢性阻塞性肺疾病模型的影响及其机制:建立体外HBE细胞模型和体内大鼠模型模拟慢性阻塞性肺病,通过多种实验方法检测RTA-408对慢性阻塞性肺病的影响:结果表明:RTA-408在体内和体外均能激活Nrf2。RTA-408通过激活Nrf2/HO-1通路,抑制NF-κB和IFN-γ通路,缓解慢性阻塞性肺疾病模型大鼠HBE细胞和PM2.5暴露细胞的炎症和氧化应激,对逆转慢性阻塞性肺疾病的细胞损伤和延缓疾病进展起到治疗作用。此外,在体外实验中,沉默 Nrf2 可消除 RTA-408 对 COPD 细胞模型的保护作用,这也证实了 RTA-408 的作用:我们的结论是,RTA-408 作为一种治疗慢性阻塞性肺病的新策略非常值得考虑,而且还可能具有积极的预防作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vivo and in vitro Models of PM2.5 Induced COPD: Focus on the Role of RTA-408.

Introduction: Inflammation and oxidative stress are important factors in the pathogenesis of Chronic obstructive pulmonary disease (COPD). Current treatments for COPD focus on improving symptoms caused by inflammation rather than curing the disease, therefore, emerging research focusing on upstream pathways may help develop effective treatments. Epidemiological investigations have shown that exposure to fine particulate matter (PM2.5) can cause lung inflammation and oxidative stress through nuclear factor NF-E2-associated factor (Nrf2) pathway, leading to COPD. Nrf2 is an important transcription factor regulating anti-inflammatory and antioxidant stress, and its abnormal expression level or changes in transcriptional activity are related to the occurrence and development of COPD. Omaviloxone - RTA-408, a synthetic oleanane triterpene that acts as an Nrf2 activator, RTA-408 may play an important role in COPD.

Purpose: In this study, PM2.5 was used to establish HBE cell model in vitro and rat model in vivo to simulate COPD, and the effect of Nrf2 activator RTA-408 on PM2.5-induced COPD model and its mechanism were investigated.

Patients and methods: The HBE cell model in vitro and rat model in vivo were established to simulate COPD, and the effect of RTA-408 on COPD was detected by various experimental methods.

Results: The results showed that RTA-408 could activate Nrf2 both in vivo and in vitro. By activating Nrf2/HO-1 pathway, RTA-408 inhibits NF-κB and IFN-γ pathways, alleviates inflammation and oxidative stress of HBE cells in COPD model rats and PM2.5 exposed cells, and plays a therapeutic role in reversing cell damage and delaying disease progression in COPD. In addition, in vitro experiments, silencing Nrf2 eliminated the protective effect of RTA-408 on COPD cell models, which also confirmed the role of RTA-408.

Conclusion: We conclude that RTA-408 is well worth considering as a new strategy for the treatment of COPD, and may also have a positive preventive effect.

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来源期刊
CiteScore
4.80
自引率
10.70%
发文量
372
审稿时长
16 weeks
期刊介绍: An international, peer-reviewed journal of therapeutics and pharmacology focusing on concise rapid reporting of clinical studies and reviews in COPD. Special focus will be given to the pathophysiological processes underlying the disease, intervention programs, patient focused education, and self management protocols. This journal is directed at specialists and healthcare professionals
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