孕期PM2.5暴露影响子代大脑发育中HMGB1/NF-κB通路的作用及机制研究

摘要
图/表
参考文献(20)
相关文章 (8)

全文: PDF (628 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的探讨孕期PM2.5暴露影响子代大脑发育中HMGB1/NF-κB p65通路的作用。方法 40只昆明小鼠孕鼠随机分5组，每组8只。气管滴注法向对照组注30 μL PBS，PM2.5低、中、高剂量组各注0.25920、1.56695、3.45600 μg/μL PM2.5混悬液30 μL，孕期每3天注1次，共7次。空白组无处理。ELISA法检测子代大脑皮层肿瘤坏死因子-α（TNF-α）、γ-干扰素（IFN-γ）、高迁移率族蛋白1（HMGB1）、核因子κB p65（NF-κB p65）浓度；Western blot、RT-PCR法检测HMGB1、NF-κB p65蛋白及mRNA变化。结果 ELISA示与对照组相比，高、中剂量组IFN-γ、NF-κB p65升高而HMGB1下降（P < 0.05），高剂量组TNF-α升高（P < 0.05）。Western blot示高、中剂量组与对照组相比，HMGB1下降且NF-κB p65上升（P < 0.05）。PCR示HMGB1 mRNA无变化，高剂量组NF-κB p65 mRNA高于对照组（P < 0.05）。结论孕期PM2.5暴露使子代鼠大脑皮层产生炎症，HMGB1/NF-κB通路可能起重要作用。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	李文燕1 郭亚楠1 郑昕蕊1 张红霞1 于丽1 江洪2

关键词 ：大脑皮层, PM2.5, &gamma, -干扰素, 肿瘤坏死因子-&alpha, 高迁移率族蛋白1, 核因子&kappa, B p65, 子代鼠

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.

Key words： Cerebral cortex PM2.5 IFN-γ TNF-α HMGB1 NF-κB p65 Offspring mice

基金资助:山东省自然科学基金资助项目（ZR2014JL016）。

通讯作者: 于丽（1976-），女，博士，教授，硕士研究生导师。江洪（1967-），女，硕士研究生导师，主任医师；研究方向：围生医学。

作者简介: 李文燕（1987.2-），女，潍坊医学院2015级妇产科学专业在读硕士研究生；研究方向：围生医学。

引用本文:

李文燕1 郭亚楠1 郑昕蕊1 张红霞1 于丽1 江洪2. 孕期PM2.5暴露影响子代大脑发育中HMGB1/NF-κB通路的作用及机制研究[J]. 中国医药导报, 2018, 15(10): 22-24,28.
LI Wenyan1 GUO Ya'nan1 ZHENG Xinrui1 ZHANG Hongxia1 YU Li1 JIANG Hong2. Mechanism of HMGB1/NF-κB signal pathway affecting cerebral development of offspring mice after exposure to PM2.5 during pregnancy. 中国医药导报, 2018, 15(10): 22-24,28.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2018/V15/I10/22

[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.