Tseng Chia-Yi, Chung Meng-Chi, Wang Jhih-Syuan, Chang Yu-Jung, Chang Jing-Fen, Lin Chin-Hung, Hseu Ruey-Shyang, Chao Ming-Wei
* Department of Biomedical Engineering.
‡ Department of Bioscience Technology, Chung Yuan Christian University Taoyuan City 32023, Taiwan.
Am J Chin Med. 2016;44(2):355-76. doi: 10.1142/S0192415X16500208.
Epidemiological studies show increased particulate matter (PM[Formula: see text]) particles in ambient air are correlated with increased myocardial infarctions. Given the close association of capillaries and alveoli, the dysfunction is caused when inhaled PM[Formula: see text] particles come in close proximity to capillary endothelial cells. We previously suggested that the inhalation of PM[Formula: see text] diesel exhaust particles (DEP) induces oxidative stress and upregulates the Nrf2/HO-1 pathway, inducing vascular permeability factor VEGFA secretion, which results in cell-cell adherens junction disruption and PM[Formula: see text] transmigratation into circulation. Here, we minimized the level that PM[Formula: see text] traveled in the bloodstream by pre-supplementing with a traditional Chinese medicine (TCM) Ganoderma tsugae DMSO extract (GTDE) prior to PM[Formula: see text] exposure. Our results show that PM[Formula: see text] caused alterations in enzyme activities and cellular anti-oxidant balance. We found decreased glutathione levels, a reduced cellular redox ratio, increased ROS generation and cytotoxicity in the cellular fractions. The oxidative stress caused DNA damage and apoptosis, likely causing downstream molecular events that trigger vasculature permeabilization and, eventually, cardiovascular disorders. Our results show long-term GTDE treatment increased endogenous glutathione level, while PM[Formula: see text]-reduced glutathione levels and the cellular redox ratio. GTDE was protective against the genotoxic and apoptotic effects initiated by PM[Formula: see text] oxidative stress. Vascular permeability revealed that PM[Formula: see text] only accumulated on the surface of cells after GTDE treatment; no penetration was detected. After two weeks of GTDE treatment, VEGFA secretion was significantly reduced in human umbilical vein endothelial cells (HUVEC) and endothelial cell migration was blocked. Our results suggest GTDE prevents PM[Formula: see text] transmigration into the bloodstream, and the resultant dysfunction, by inhibiting oxidative stress production and endothelial permeability.
流行病学研究表明，环境空气中颗粒物（PM[公式：见正文]）的增加与心肌梗死的增加相关。鉴于毛细血管和肺泡密切相关，当吸入的PM[公式：见正文]颗粒靠近毛细血管内皮细胞时就会导致功能障碍。我们之前曾提出，吸入PM[公式：见正文]柴油废气颗粒（DEP）会诱导氧化应激并上调Nrf2/HO-1途径，诱导血管通透性因子VEGFA分泌，从而导致细胞间黏附连接破坏以及PM[公式：见正文]迁移到循环系统中。在此，我们通过在暴露于PM[公式：见正文]之前预先补充中药云芝二甲基亚砜提取物（GTDE），将PM[公式：见正文]在血液中传播的水平降至最低。我们的结果表明，PM[公式：见正文]导致了酶活性和细胞抗氧化平衡的改变。我们发现细胞组分中的谷胱甘肽水平降低、细胞氧化还原比降低、活性氧生成增加以及细胞毒性增加。氧化应激导致DNA损伤和细胞凋亡，可能引发下游分子事件，进而触发血管通透性增加并最终导致心血管疾病。我们的结果表明，长期GTDE治疗可提高内源性谷胱甘肽水平，而PM[公式：见正文]会降低谷胱甘肽水平和细胞氧化还原比。GTDE对PM[公式：见正文]氧化应激引发的遗传毒性和凋亡效应具有保护作用。血管通透性显示，GTDE处理后PM[公式：见正文]仅积聚在细胞表面；未检测到穿透现象。GTDE处理两周后，人脐静脉内皮细胞（HUVEC）中的VEGFA分泌显著减少且内皮细胞迁移受到阻断。我们的结果表明，GTDE通过抑制氧化应激产生和内皮通透性来防止PM[公式：见正文]迁移到血液中以及由此产生的功能障碍。
