PM2.5 诱导 COPD 的体内和体外模型：聚焦于 RTA-408 的作用。
In vivo and in vitro Models of PM2.5 Induced COPD: Focus on the Role of RTA-408.
机构信息
Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Department of Respiratory and Critical Care Medicine, Huabei Petroleum Administration Bureau General Hospital, Renqiu, Hebei, People's Republic of China.
出版信息
Int J Chron Obstruct Pulmon Dis. 2024 Oct 9;19:2239-2257. doi: 10.2147/COPD.S475281. eCollection 2024.
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.
简介
炎症和氧化应激是慢性阻塞性肺疾病（COPD）发病机制中的重要因素。目前 COPD 的治疗方法侧重于改善炎症引起的症状，而不是治愈疾病，因此，针对上游途径的新兴研究可能有助于开发有效的治疗方法。流行病学调查表明，细颗粒物（PM2.5）暴露可通过核因子 NF-E2 相关因子（Nrf2）途径引起肺部炎症和氧化应激，导致 COPD。Nrf2 是调节抗炎和抗氧化应激的重要转录因子，其异常表达水平或转录活性变化与 COPD 的发生和发展有关。Omalixolone-RTA-408 是一种合成的齐墩果酸三萜，作为 Nrf2 激活剂，RTA-408 可能在 COPD 中发挥重要作用。
目的
本研究采用 PM2.5 建立体外 HBE 细胞模型和体内大鼠模型模拟 COPD，并探讨 Nrf2 激活剂 RTA-408 对 PM2.5 诱导的 COPD 模型的作用及其机制。
患者和方法
建立体外 HBE 细胞模型和体内大鼠模型模拟 COPD，采用多种实验方法检测 RTA-408 对 COPD 的作用。
结果
结果表明，RTA-408 可在体内和体外激活 Nrf2。通过激活 Nrf2/HO-1 通路，RTA-408 抑制 NF-κB 和 IFN-γ 通路，减轻 COPD 模型大鼠和 PM2.5 暴露细胞中 HBE 细胞的炎症和氧化应激，在逆转 COPD 细胞损伤和延缓疾病进展方面发挥治疗作用。此外，体外实验中，沉默 Nrf2 消除了 RTA-408 对 COPD 细胞模型的保护作用，这也证实了 RTA-408 的作用。
结论
我们得出结论，RTA-408 作为 COPD 治疗的一种新策略是值得考虑的，并且可能对预防也有积极作用。
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