产前PM2.5暴露通过Nrf2/NLRP3通路诱导子代高血压

IF 8.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Xinyuan Zhang,Boping Yang,Mengyuan Li,Xiaoxiao Guo,Yilin Li,Xiangqian Gao,Lei Zhang,Ningxiao Jiang,Shinan Zhang,Huishu Xu,Baolin Zhang,Yanlin Wang,Yingjiang Xu,Gaofeng Qin,Bin Liu,Ping Yi,Lei Han
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引用次数: 0

摘要

背景孕期的不利因素可显著增加成年后代高血压的发病率。交感神经系统的激活与高血压的发生发展密切相关。方法建立产前细颗粒物暴露致子代高血压模型,评价交感神经系统激活的作用。定量免疫荧光和Western blot分析评估激活和抑制交感神经元的水平。使用可乐定和肾交感神经去神经术评估中枢和周围交感神经系统的影响。此外,我们还分析了侧脑室区小胶质细胞的激活情况和Nrf2(核因子e2相关因子)/ NLRP3 (NLR家族pyrin -containing 3)信号通路的表达情况。结果大鼠成年子代神经异常活跃,交感神经系统异常活跃。中枢交感神经系统和肾去神经的特异性抑制有效地逆转了产前细颗粒物引起的成年后代血压升高。此外,氧化应激过度激活和室旁核小胶质细胞介导的炎症是暴露于产前细颗粒物的成年后代中枢交感神经活动增加的原因。此外,我们证实了Nrf2/NLRP3信号通路在成年后代室旁核氧化应激和炎症激活中的关键作用。结论总的来说,产前细颗粒物暴露可通过Nrf2/NLRP3信号通路诱导室旁核小胶质细胞过度炎症和氧化应激,导致中枢和外周交感神经过度激活,导致高血压和左室肥厚。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prenatal PM2.5 Exposure Induces Offspring Hypertension via Nrf2/NLRP3 Pathway.
BACKGROUND Adverse factors during pregnancy can significantly increase the incidence of hypertension in adult offspring. Activation of the sympathetic nervous system is closely associated with the development and progression of hypertension. METHODS We established a model of offspring hypertension induced by prenatal fine particulate matter exposure to evaluate the role of the sympathetic nervous system activation. Quantitative immunofluorescence and Western blot analysis were used to assess the levels of activated and inhibitory sympathetic neurons. The effects of the central and peripheral sympathetic nervous systems were evaluated using clonidine and renal sympathetic denervation. In addition, the activation of microglia in the lateral ventricle region and the expression of the Nrf2 (nuclear factor E2-related factor)/ NLRP3 (NLR family pyrin domain-containing 3) signaling pathway were analyzed. RESULTS The adult offspring showed increased neuronal hyperactivity and sympathetic nervous system activity. Specific inhibition of the central sympathetic nervous system and renal denervation effectively reversed the prenatal fine particulate matter-induced blood pressure elevation in adult offspring. In addition, overactivation of oxidative stress and microglia-mediated inflammation in the paraventricular nucleus was responsible for increased central sympathetic activity in the adult offspring exposed to prenatal fine particulate matter. Furthermore, we confirmed the critical role of the Nrf2/NLRP3 signaling pathway in oxidative stress and inflammation activation in the paraventricular nucleus of adult offspring. CONCLUSIONS Overall, prenatal fine particulate matter exposure induces excessive inflammation and oxidative stress in paraventricular nucleus microglia through the Nrf2/NLRP3 signaling pathway, resulting in central and peripheral sympathetic overactivation, leading to hypertension and left ventricular hypertrophy.
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来源期刊
Hypertension
Hypertension 医学-外周血管病
CiteScore
15.90
自引率
4.80%
发文量
1006
审稿时长
1 months
期刊介绍: Hypertension presents top-tier articles on high blood pressure in each monthly release. These articles delve into basic science, clinical treatment, and prevention of hypertension and associated cardiovascular, metabolic, and renal conditions. Renowned for their lasting significance, these papers contribute to advancing our understanding and management of hypertension-related issues.
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