PM2.5与甲醛联合暴露对出生早期大鼠自闭症样病变的影响
Effects of Combined Exposure to PM2.5 and Formaldehyde on Autism-like Phenotypes in Early Birth Rats
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摘要: 为探究典型室外、室内空气污染物PM2.5和甲醛（FA）联合暴露对出生早期大鼠自闭症（ASD）样病变的影响及作用机制。以出生7 d的SD大鼠为受试动物，设置空白对照组、PM2.5暴露组（0.1351 mg·kg-1·d-1）、FA暴露组（0.1085 mg·kg-1·d-1）、联合暴露组（0.1351 mg·kg-1·d-1 PM2.5+0.1085 mg·kg-1·d-1）对其进行连续14 d的鼻腔内暴露。通过三箱社交试验、埋珠试验、旷场试验和Morris水迷宫试验对小鼠行为学变化进行检测，观察小鼠脑组织病理变化及胶质细胞激活情况。对小鼠脑组织中氧化应激、炎症因子表达水平和MAPK信号通路关键分子P38、JNK磷酸化情况进行检测。结果显示，PM2.5和FA联合暴露后小鼠出现社交障碍、重复刻板行为、认知和探索能力下降等典型ASD样行为变化，脑组织中活性氧（ROS）、丙二醛（MDA）和4-羟基壬烯醛（4-HNE）水平上升；谷胱甘肽（GSH）含量和超氧化物歧化酶活性（SOD）下降；促炎症因子（IL-2、MCP-1、IL-6、IL-17、INF-γ、sTNFRI、TNF-α、MCP-5）表达量增加；P38和JNK磷酸化水平升高。研究表明，0.1351 mg·kg-1·d-1 PM2.5、0.1085 mg·kg-1·d-1 FA暴露并未对出生早期大鼠产生显著影响，但二者联合暴露会导致大鼠出现ASD样病变，MAPK信号通路激活、脑组织氧化应激和神经炎症水平的升高参与了联合暴露的致损伤过程。Abstract: To investigate the effects and mechanism of combined exposure of typical outdoor and indoor air pollutants PM2.5 and formaldehyde (FA) on autism (ASD)-like lesions in early birth rats. 7 days old SD rats were used as experimental animals and randomly divided into control group, PM2.5 exposure group (0.1351 mg·kg-1·d-1), FA exposure group (0.1085 mg·kg-1·d-1) and combined exposure group (0.1351 mg·kg-1·d-1 PM2.5+0.1085 mg·kg-1·d-1 FA), rats were subjected to nasal exposure for 14 consecutive days. The behavioral changes of mice were detected by three-chambered social test, marble burying test, open field test and Morris water maze test, and the pathological changes of brain tissues and the activation of glial cells were observed. The levels of oxidative stress, inflammatory factors expression and phosphorylation of key molecules of MAPK signaling pathway P38 and JNK in rat brain tissues were detected. The results showed that rat with combined exposure to PM2.5 and FA showed typical ASD-like behavioral changes such as social disturbance, repetitive stereotyped behavior, cognitive and exploration decline. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) in brain tissues increased. Glutathione (GSH) content and superoxide dismutase (SOD) activity decreased. The expression of pro-inflammatory factors (IL-2, MCP-1, IL-6, IL-17, INF-γ, sTNFRI, TNF-α, MCP-5) increased. The phosphorylation levels of P38 and JNK increased. Studies have shown that 0.1351 mg·kg-1·d-1 PM2.5 and 0.1085 mg·kg-1·d-1 FA exposure have no significant effects on early birth rats, but combined exposure of PM2.5 and FA can lead to ASD-like phenotype in rats. Activation of MAPK signaling pathway, increased levels of oxidative stress and neuroinflammation in brain tissue participate in the damage induced by combined exposure.
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Key words:
- PM2.5 /
- formaldehyde /
- early birth rats /
- autism /
- oxidative stress /
- neuroinflammation /
- MAPK pathway
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