School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang 453003, PR China; Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, PR China.
School of Public Health, Xinxiang Medical University, 601 Jinsui Road, Xinxiang 453003, PR China.
Chemosphere. 2018 May;199:538-545. doi: 10.1016/j.chemosphere.2018.02.082. Epub 2018 Feb 14.
Hepatic fibrosis, characterized by an excessive accumulation of extracellular matrix, is associated with toxic substance exposure, chronic infections, mechanical injury, airborne fine particulate matter (PM) exposure and metabolic disease. This study aimed to investigate the effect and mechanism of long-term, real-world airborne particulate matter (PM) exposure on hepatic fibrosis and further explored whether combination treatment of PM exposure and high-fat diet (HFD) aggravate the adverse effects in mice.
Six-week-old male C57BL/6J mice fed with either a standard chow diet (STD) or an HFD were treated with either filtered air (FA) or PM for 18 weeks. Metabolic parameters, histological examination, gene expression analysis, and Western blot analysis were utilized to measure the effect and mechanism of PM exposure on hepatic fibrosis and to further analyze the synergistic effect of HFD. Subchronic airborne PM exposure induces hepatic fibrosis in mice, and combination treatment of PM exposure and HFD accelerate the adverse effect. Meanwhile, subchronic exposure to real-world PM increased the level of hepatic ROS, and the expression of endoplasmic reticulum (ER) stress markers (GRP78 and CHOP), p-SMAD2 and p-SMAD3, as well as up-regulated TGFβ and collagen 1 in liver tissues. Furthermore, PM exposure and HFD displayed the synergistic effects on these changes in liver.
Our findings indicate that airborne PM exposure aggravates HFD -induced hepatic fibrosis. The ROS-ER stress-TGFβ/SMADs regulatory axis mediates the effects of airborne PM exposure on accelerating hepatic fibrosis.
肝纤维化的特征是细胞外基质的过度积累，与有毒物质暴露、慢性感染、机械损伤、空气细颗粒物（PM）暴露和代谢性疾病有关。本研究旨在探讨长期真实环境空气 PM 暴露对肝纤维化的影响及其机制，并进一步探讨 PM 暴露与高脂肪饮食（HFD）联合治疗是否会加重小鼠的不良影响。
将 6 周龄雄性 C57BL/6J 小鼠分别用标准饲料（STD）或高脂肪饲料（HFD）喂养，然后用过滤空气（FA）或 PM 处理 18 周。利用代谢参数、组织学检查、基因表达分析和 Western blot 分析来衡量 PM 暴露对肝纤维化的影响及其机制，并进一步分析 HFD 的协同作用。亚慢性空气 PM 暴露可诱导小鼠肝纤维化，PM 暴露和 HFD 的联合治疗加速了不良影响。同时，亚慢性暴露于实际 PM 增加了肝组织中 ROS 的水平，以及内质网（ER）应激标志物（GRP78 和 CHOP）、p-SMAD2 和 p-SMAD3 的表达，并上调了 TGFβ 和胶原 1。此外，PM 暴露和 HFD 对这些肝组织变化表现出协同作用。
我们的研究结果表明，空气 PM 暴露加重了 HFD 诱导的肝纤维化。ROS-ER 应激-TGFβ/SMADs 调节轴介导了空气 PM 暴露对加速肝纤维化的影响。
