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| Mechanism of HMGB1/NF-κB signal pathway affecting cerebral development of offspring mice after exposure to PM2.5 during pregnancy |
| LI Wenyan1 GUO Ya'nan1 ZHENG Xinrui1 ZHANG Hongxia1 YU Li1 JIANG Hong2 |
1.Institute of Clinical Medicine, Weifang Medical College, Shandong Province, Weifang 261000, China;
2.Department of Gynaecology and Obstetrics, Weifang People′s Hospital, Shandong Province, Weifang 261000, China |
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Abstract Objective To investigate the mechanism of HMGB1/NF-κB signal pathway affecting cerebral development of offspring after exposure to PM2.5 during pregnancy. Methods Fourty pregnant Kunming mice were randomly divided into 5 groups, 8 rats in each group. PM2.5 low-dose group, medium-dose group and high-dose group were instilled 30 μL PM2.5 suspension of 0.25920, 1.56695, 3.45600 μg/μL respectively by improved technique for rapid intratracheal instillation. The control group was instilled PBS of the same volume. The blank group received no treatments. Mice were instilled tracheally once every 3 days for 7 times during pregnancy. ELISA was used to measure the levels of TNF-α, IFN-γ, HMGB1 and NF-κB p65 in the cerebral cortex of offspring mice. Western blot and RT-PCR were used to detect the protein and mRNA expression of HMGB1 and NF-κB p65. Results ELISA showed that compared with the control group, the levels of IFN-γ, NF-κB p65 and HMGB1 in the high and middle dose groups were significantly lower (P < 0.05); high-dose group TNF-α increased (P < 0.05). Western blot showed that HMGB1 decreased and NF-κB p65 increased in the high and middle dose groups compared with the control group (P < 0.05). PCR showed HMGB1 mRNA unchanged; high-dose group NF-κB p65 mRNA was higher than the control group (P < 0.05). Conclusion PM2.5 exposure during pregnancy may cause inflammation in the cerebral cortex of offspring mice, and HMGB1/NF-κB pathway may play an important role.
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| [1] Genc S，Zadeoglulari Z，Fuss SH，et al. The Adverse Effects of Air Pollution on the Nervous System [J]. J Toxicol，2012， 2012：782462.
[2] Verina T，Kiihl SF，Schneider JS，et al. Manganese exposure induces microglia activation and dystrophy in the substantia nigra of non-human primates [J]. Neurotoxicology，2011， 32（2）：215-226.
[3] 郑昕蕊，赵会，田换兵，等.妊娠期PM2.5暴露影响子代鼠主要脏器发育[J].中国组织化学与细胞化学杂志，2017，26（4）：365-372.
[4] 王育梅.大气颗粒物对小鼠胚胎发育的影响[D].福州：福建医科大学，2009.
[5] Yang G，Wang Y，Zeng Y，et al. Rapid health transition in China，1990-2010：findings from the Global Burden of Disease Study 2010 [J]. Lancet，2013，381（9882）：1987-2015.
[6] Fagundes LS，Fleck Ada S，Zanchi AC，et al. Direct contact with particulate matter increases oxidative stress in different brain structures [J]. Inhal Toxicol，2015，27（10）：462-467.
[7] Berlo D，Albrecht C，Knaapen AM，et al. Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain [J]. Archives of Toxicology，2010，84（7）：553-562.
[8] Srimathi K，Dawn P，Misra J，et al. Exposures to airborne particulate matter and adverse perinatal outcomes：a biologically plausible mechanistic framework for exploring potential [J]. Environ Health Perspect，2006，114（11）：1636-1642.
[9] Takeda K，Tsukue N，Yoshida S. Endocrine-disrupting activity of chemical in diesel exhaust and diesel exhaust particles [J]. Environ Sci，2004，11（1）：33-45.
[10] Bolton JL，Huff NC，Smith SH，et al. Maternal stress and effects o1 prenatal air pollution on offspring mental health outcomes in mice [J]. Environmental Health Perspec?鄄tives，2013，121（9）：1075-1082.
[11] Wan H，Bloom O，Zhang M，et al. HMG-1 as a late mediator of endotoxin lethality in mice [J]. Science，1999， 285（5425）：248-251.
[12] Abraham E，Arcaroli J，Carmody A，et al. HMG-1 as a mediator of acute lung inflammation [J]. J Immunol，2000， 165（6）：2950-2954.
[13] Taniguchi N，Kawahara K，Yone K，et al. High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine [J]. Arthritis Rheum，2003，48（4）：971-981.
[14] Matsuoka N，Itoh T，Watarai H，et al. High-mobility group box1 is involved in the initial events of early loss of transplanted islets in mice [J]. J Clin Invest，2010，120（3）：735-743.
[15] Sims GP，Rowe DC，Rietdijk ST，et al. HMGBl and RAGE in inflammation and cancer [J]. Annu Rev Immunol，2010， 28（1）：367-388.
[16] Park JS，Gamboni-Robertson F，He Q，et al. High mobility group box1 protein interacts with multiple Toll-like receptors [J]. Am J Physiol Cell Physiol，2006，290（3）：C917-C924.
[17] Luan ZG，Zhang H，Yang PT，et al. HMGBl activates nuclear factor-κB signaling by RAGE and increases the production of TNF-α in human umbilical vein endothelial cells [J]. Immunobiology，2010，215（12）：956-962.
[18] 朱明光，常雅萍.高迁移率族蛋白B1的致炎细胞因子作用研究进展[J].国际免疫学杂志，2006，29（4）：257-260.
[19] 殷益宏，任明山.髙迁移率族蛋白B1与脑缺血[J].国际脑血管疾病，2010，18（3）：228-230.
[20] Gardella S，Andrei C，Ferrera D，et al. The nuclear protein HMGB1 is secreted by monocytes via a non-classical，vesicle-mediated secretory pathway [J]. EMBO Rep，2002， 3（10）：995-1001. |
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