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炎症促进/抑制失衡在同时暴露于细颗粒物和二氧化硫的大鼠脑内β淀粉样蛋白42(Aβ42)蓄积中的作用

The role of pro-/anti-inflammation imbalance in Aβ42 accumulation of rat brain co-exposed to fine particle matter and sulfur dioxide.

作者信息

Yang Zhenhua, Chen Yunzhu, Zhang Yuexia, Li Ruijin, Dong Chuan

机构信息

a Institute of Environmental Science , Shanxi University , Taiyuan , China.

出版信息

Toxicol Mech Methods. 2017 Oct;27(8):568-574. doi: 10.1080/15376516.2017.1337256. Epub 2017 Jun 20.

Abstract

Taiyuan is a center of coal-based electricity production and many chemicals industries, where mixtures of sulfur dioxide (SO) and particulate matter may be more prominent. The focus of the present study was to determine if there is a link between adverse effects in the brain and the combined-exposure to SO and fine particulate matter (PM). Rats were exposed alternately to PM with different dosages (1.5, 6.0 and 24.0 mg/kg body weight) and SO at the level of 5.6 mg/m. The results showed that the combined exposure to PM and SO enhanced the mRNA expression and protein level of TNF-α and IL-6 in rat cortex and hippocampus relative to the control, SO and PM alone. Instead, TGF-β1 mRNA and protein level were down-regulated in the brain. Additionally, PM at medium and/or high dose caused marked increase in Aβ42 level and PM + SO induced further increase of Aβ42 level in the cortex and hippocampus. It suggests that SO and PM can synergistically exert inflammation responses and induce Aβ42 accumulation in the brain. Also, it is notable that the Aβ42 accumulation of rat cortex and hippocampus were closely associated with pro-/anti-inflammatory cytokines ratio. These results clearly demonstrated that the combined exposure to PM and SO can induce the imbalance of pro-/anti-inflammatory cytokine, resulting in Aβ42 accumulation of rat brain cortex and hippocampus.

摘要

太原是煤电生产和众多化工产业的中心,二氧化硫(SO)和颗粒物的混合物可能更为突出。本研究的重点是确定大脑中的不良反应与二氧化硫和细颗粒物(PM)的联合暴露之间是否存在关联。将大鼠交替暴露于不同剂量(1.5、6.0和24.0毫克/千克体重)的颗粒物以及5.6毫克/立方米水平的二氧化硫中。结果表明,与对照组、单独的二氧化硫组和单独的颗粒物组相比,颗粒物与二氧化硫的联合暴露增强了大鼠皮层和海马体中肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的mRNA表达和蛋白质水平。相反,大脑中转化生长因子-β1(TGF-β1)的mRNA和蛋白质水平下调。此外,中高剂量的颗粒物导致淀粉样β蛋白42(Aβ42)水平显著升高,颗粒物与二氧化硫联合暴露导致皮层和海马体中Aβ42水平进一步升高。这表明二氧化硫和颗粒物可协同引发炎症反应并诱导大脑中Aβ42的积累。同样值得注意的是,大鼠皮层和海马体中Aβ42的积累与促炎/抗炎细胞因子的比例密切相关。这些结果清楚地表明,颗粒物与二氧化硫的联合暴露可导致促炎/抗炎细胞因子失衡,从而导致大鼠大脑皮层和海马体中Aβ42的积累。

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