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β-胡萝卜素通过 Nrf2 依赖性途径发挥对 PM2.5 颗粒诱导的肺损伤的治疗作用。

Therapeutic potential of bixin in PM2.5 particles-induced lung injury in an Nrf2-dependent manner.

机构信息

School of Public Health, Medical College of Soochow University, 199 Ren'ai Road, Suzhou 215123, Jiangsu, China.

Medical College of Soochow University, 199 Ren'ai Road, Suzhou 215123, Jiangsu, China.

出版信息

Free Radic Biol Med. 2018 Oct;126:166-176. doi: 10.1016/j.freeradbiomed.2018.08.015. Epub 2018 Aug 16.

DOI:10.1016/j.freeradbiomed.2018.08.015
PMID:30120979
Abstract

Fine particulate matter (PM 2.5) is a well-known air pollutant threatening public health. Studies has confirmed that long-term exposure to the particles could reduce the pulmonary function, cause exacerbation of asthma and chronic obstructive pulmonary disease, and increase incidence and mortality of lung cancer. Bixin is a natural compound that is widely used as a food additive. Our previous studies demonstrated that bixin i.p. administration could protect against particles intratracheal exposure (56 days)-induced lung injury in an Nrf2-dependent manner. But the detail mechanisms are still unclarified. Our current study aimed to explore the further therapeutic potential and mechanism of bixin to slow the progression of lung injury and inflammation in vivo and in vitro. The results from the in vivo study showed that bixin treatment attenuated the accumulation of inflammatory cells, decreased the levels of tissue apoptosis, and increase the ability of cell proliferation. Besides that, bixin also could regulate the expression of MMP9, TGFβ1, and its downstream Fibronectin (FN), along with activation of Nrf2 signals. In vitro experiments in human bronchial epithelial cells demonstrated that Nrf2 activated by bixin contributes to tissue repair by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis, which may be partially through modulating the expression of MMP9, TGFβ1, and FN. This study provides convincing experimental evidences that bixin could be used therapeutically to promote tissue repair and improve pulmonary injury induced by particles exposure.

摘要

细颗粒物(PM 2.5)是一种众所周知的威胁公众健康的空气污染物。研究证实,长期暴露于这些颗粒中可能会降低肺功能,导致哮喘和慢性阻塞性肺疾病恶化,并增加肺癌的发病率和死亡率。胭脂树橙是一种广泛用作食品添加剂的天然化合物。我们之前的研究表明,胭脂树橙腹腔内给药可以以 Nrf2 依赖的方式保护颗粒气管内暴露(56 天)引起的肺损伤。但详细机制尚不清楚。本研究旨在探讨胭脂树橙在体内和体外减缓肺损伤和炎症进展的进一步治疗潜力和机制。体内研究结果表明,胭脂树橙治疗可减轻炎症细胞的积聚,降低组织细胞凋亡水平,并增加细胞增殖能力。此外,胭脂树橙还可以调节 MMP9、TGFβ1 及其下游纤维连接蛋白(FN)的表达,并激活 Nrf2 信号。人支气管上皮细胞的体外实验表明,胭脂树橙激活的 Nrf2 通过减轻氧化应激、增加增殖和迁移、减少凋亡来促进组织修复,这可能部分是通过调节 MMP9、TGFβ1 和 FN 的表达。这项研究提供了令人信服的实验证据,表明胭脂树橙可用于治疗,以促进组织修复并改善颗粒暴露引起的肺损伤。

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