摘要
近年来,已有大量的流行病学调查证实,孕产妇暴露于PM_(2.5)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PM_(2.5)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PM_(2.5)组(1.5 mg/kg PM_(2.5))、高剂量PM_(2.5)组(7.5 mg/kg PM_(2.5))、DMF对照组(生理盐水+50 mg/kg DMF)和DMF干预组(7.5 mg/kg PM_(2.5)+50 mg/kg DMF)。大鼠每2 d染毒1次,共持续40 d。经PM_(2.5)暴露后,高剂量PM_(2.5)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PM_(2.5)组(P<0.01),能够明显缓解PM_(2.5)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PM_(2.5)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PM_(2.5)组和高剂量PM_(2.5)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PM_(2.5)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PM_(2.5)对胎盘造成的氧化损伤,提高机体的抗氧化能力。
In recent years,a large number of epidemiological investigations have confirmed that maternal exposure to PM_(2.5) may increase the risk of pregnancy complications and adverse pregnancy outcomes.The aim of this study is to investigate the damage of PM_(2.5) exposure before pregnancy to the placenta of rats and the underlying regulatory mechanism of dimethyl fumarate(DMF).Forty 6-week-old SPF grade female SD rats were randomly divided into the control group(normal saline),the low-dose PM_(2.5) group(1.5 mg/kg PM_(2.5)),the high-dose PM_(2.5) group(7.5 mg/kg PM_(2.5)),a DMF control group(normal saline+50 mg/kg DMF),and the DMF intervention group(7.5 mg/kg PM_(2.5)+50 mg/kg DMF).Rats were exposed to PM_(2.5) once every two days for a total of a 40 day period.After exposure to PM_(2.5),the number and average body length of fetuses in the high-dose PM_(2.5) group were significantly lower than those in the control group(P<0.05),as well as the activity of superoxide dismutase(SOD),total antioxidant capacity(T-AOC)and the concentration of interleukin-10(IL-10)in placental tissues in the high-dose PM_(2.5) 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 PM_(2.5) group(P<0.01),this suggested that DMF treatment might alleviate the oxidative damage induced by PM_(2.5).The H&E staining results of rat placental tissues showed that there was a varying degree of reduction in the number of blood cells in the labyrinthine area of the PM_(2.5) exposure group.The high-dose PM_(2.5) 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 choroids.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 PM_(2.5) group and high-dose PM_(2.5) group were lower than those in the control group(P<0.01).Compared with the high-dose PM_(2.5) 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 PM_(2.5) exposure before pregnancy and improve the body antioxidant capacity through the Nrf2/HO-1 signaling pathway.
作者
李江珂
董恩恒
张丰泉
张俊强
伍源
LI Jiang-Ke;DONG En-Heng;ZHANG Feng-Quan;ZHANG Jun-Qiang;WU Yuan(Key Laboratory for Air Pollution Health Effects and Intervention of Xinxiang,School of Public Health,Xinxiang Medical University,Xinxiang 453003,Henan,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2024年第2期231-239,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
河南省高校科技创新团队支持计划(No.14IRTSTHN017)资助。
关键词
细颗粒物
富马酸二甲酯
胎盘
氧化损伤
particulate matter 2.5(PM 2.5)
dimethyl fumarate(DMF)
placenta
oxidative damage
