首页|富马酸二甲酯通过Nrf2/HO-1信号通路缓解细颗粒物对雌性大鼠胎盘的氧化损伤

富马酸二甲酯通过Nrf2/HO-1信号通路缓解细颗粒物对雌性大鼠胎盘的氧化损伤

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近年来,已有大量的流行病学调查证实,孕产妇暴露于PM2。5可能导致妊娠并发症和不良妊娠结局的风险增加。本研究旨在探讨孕前PM2。5暴露对大鼠胎盘的损伤及富马酸二甲酯(dimethyl fumarate,DMF)对其调控机制。40只6周龄SPF级雌性SD大鼠,随机分为对照组(生理盐水)、低剂量 PM2。5 组(1。5 mg/kg PM2。5)、高剂量 PM2。5 组(7。5 mg/kg PM2。5)、DMF 对照组(生理盐水+50 mg/kg DMF)和 DMF 干预组(7。5 mg/kg PM2。5+50 mg/kg DMF)。大鼠每 2 d 染毒 1 次,共持续 40 d。经PM2。5暴露后,高剂量PM2。5组胎鼠数量、胎鼠平均体长、超氧化物歧化酶(SOD)活性和总抗氧化能力(T-AOC)、白细胞介素-10(IL-10)含量明显低于对照组(P<0。05);丙二醛(MDA)含量高于对照组(P<0。05);经DMF处理后,DMF干预组的T-AOC含量显著高于高剂量PM2。5组(P<0。01),能够明显缓解PM2。5诱导的氧化损伤作用。H&E染色结果显示,暴露组胎盘组织迷路区血细胞有不同程度的减少,高剂量PM2。5组血管脉络不清晰,DMF干预组胎盘迷路区的血细胞明显增多,血管脉络清晰整齐。Western印迹结果显示,低剂量PM2。5组和高剂量PM2。5组核因子E2相关因子(Nrf2)、血红素加氧酶1(HO-1)蛋白质水平低于对照组(P<0。01),与高剂量PM25组相比,DMF干预组的Nrf2、HO-1蛋白质含量明显增高(P<0。05)。综上所述,DMF可能通过Nrf2/HO-1信号通路缓解孕前PM25对胎盘造成的氧化损伤,提高机体的抗氧化能力。
Dimethyl Fumarate Alleviates Oxidative Damage of Fine Particulate Matter to the Placenta of Female Rats through the Nrf2/HO-1 Signaling Pathway
In recent years,a large number of epidemiological investigations have confirmed that maternal exposure to PM2.5 may increase the risk of pregnancy complications and adverse pregnancy outcomes.The aim of this study is to investigate the damage of PM2.5 exposure before pregnancy to the placenta of rats and the underlying regulatory mechanism of dimethyl fumarate(DMF).Forty 6-week-old SPF grade fe-male SD rats were randomly divided into the control group(normal saline),the low-dose PM2.5 group(1.5 mg/kg PM2.5),the high-dose PM2.5 group(7.5 mg/kg PM2.5),a DMF control group(normal sa-line+50 mg/kg DMF),and the DMF intervention group(7.5 mg/kg PM2.5+50 mg/kg DMF).Rats were exposed to PM2.5 once every two days for a total of a 40 day period.After exposure to PM2.5,the number and average body length of fetuses in the high-dose PM2.5 group were significantly lower than those in the control group(P<0.05),as well as the activity of superoxide dismutase(SOD),total an-tioxidant capacity(T-AOC)and the concentration of interleukin-10(IL-10)in placental tissues in the high-dose PM2.5 group were significantly lower than those in the control group(P<0.05),while the content of malondialdehyde(MDA)was higher than that in the control group(P<0.05).After the DMF treatment,the T-AOC in the DMF intervention group was significantly higher than that in the high-dose PM2.5 group(P<0.01),this suggested that DMF treatment might alleviate the oxidative damage induced by PM2.5.The H&E staining results of rat placental tissues showed that there was a varying de-gree of reduction in the number of blood cells in the labyrinthine area of the PM2.5 exposure group.The high-dose PM2.5 group had unclear vascular choroids,while the DMF intervention group had a significant increase in the number of blood cells in the labyrinthine area of the placenta and had clear vascular cho-roids.Western blotting results showed that the protein levels of nuclear factor E2 related factor(Nrf2)and heme oxygenase-1(HO-1)in the low-dose PM2.5 group and high-dose PM2.5 group were lower than those in the control group(P<0.01).Compared with the high-dose PM2.5 group,the protein level of Nrf2 and HO-1 in the DMF intervention group was significantly increased(P<0.05).In summary,DMF may alleviate the oxidative damage to the placenta caused by PM2.5 exposure before pregnancy and improve the body antioxidant capacity through the Nrf2/HO-1 signaling pathway.

particulate matter 2.5(PM2.5)dimethyl fumarate(DMF)placentaoxidative damage

李江珂、董恩恒、张丰泉、张俊强、伍源

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新乡医学院公共卫生学院新乡市大气污染健康效应与干预重点实验室,河南新乡 453003

细颗粒物 富马酸二甲酯 胎盘 氧化损伤

河南省高校科技创新团队支持计划

14IRTSTHN017

2024

中国生物化学与分子生物学报
中国生物化学与分子生物学会 北京大学

中国生物化学与分子生物学报

CSTPCD北大核心
影响因子:0.617
ISSN:1007-7626
年,卷(期):2024.40(2)
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