Therapeutic potential of bixin in PM2.5 particles-induced lung injury in an Nrf2-dependent manner
Therapeutic potential of bixin in PM2.5 particles-induced lung injury in an Nrf2-dependent manner
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红木素以 Nrf2 依赖性方式对 PM2.5 颗粒引起的肺损伤的治疗潜力
DOI：
10.1016/j.freeradbiomed.2018.08.015
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发表时间：
2018
影响因子：
7.4
通讯作者：
Shasha Tao
中科院分区：
文献类型：
--
作者：
Hong Zhang;Lian Xue;Bingyan Li;Hailin Tian;Zengli Zhang;Shasha Tao
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，长期接触这些颗粒物会降低肺功能，导致哮喘和慢性阻塞性肺疾病加重，增加肺癌的发病率和死亡率。胭脂树红是一种天然化合物，被广泛用作食品添加剂。我们以前的研究表明，胭脂树红i.p.管理可以防止颗粒intrichelheal暴露（56天）诱导的肺损伤的Nrf2依赖性的方式。但其具体机制尚不清楚。本研究旨在探讨胭脂树橙在体内和体外延缓肺损伤和炎症进展的进一步治疗潜力和机制。在体研究结果表明，胭脂树红处理减轻了炎症细胞的积聚，降低了组织凋亡水平，并增加了细胞增殖能力。此外，胭脂树橙还能调节MMP 9、TGFβ1及其下游纤维连接蛋白（FN）的表达，沿着Nrf2信号的激活。体外人支气管上皮细胞实验表明，胭脂树橙激活的Nrf2可通过减轻氧化应激，促进细胞增殖和迁移，减少细胞凋亡而促进组织修复，其机制可能部分通过调节MMP 9、TGFβ1、FN的表达，的FN。本研究为胭脂树红促进肺组织修复、改善肺损伤提供了实验依据。
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 inflammationin vivoandin vitro. The results from thein vivostudy 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 vitroexperiments 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.