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Inhibition of Maternal c-Src Ameliorates the Male Offspring Hypertension by Suppressing Inflammation and Neurotransmitters in the Paraventricular Nucleus
Cardiovascular Toxicology ( IF 3.4 ) Pub Date : 2021-07-16 , DOI: 10.1007/s12012-021-09672-z
Qing Su 1 , Xiao-Jing Yu 1 , Qing Yang 2 , Xiao-Min Wang 1 , Wen-Jie Xia 1 , Hong-Bao Li 1 , Kai-Li Liu 1 , Qiu-Yue Yi 3 , Yu-Ming Kang 1
Affiliation  

Long-term maternal salt intake induces the hypertension in offspring. Numerous studies have also indicated that high-salt diet causes the inflammation and an imbalance in neurotransmitters in the paraventricular nucleus (PVN) which increases the blood pressure and sympathetic activity. This study aimed to explore whether maternal salt intake induces hypertension in their male offspring by increasing the inflammation and changing the neurotransmitters balance in the paraventricular nucleus of offspring. This study includes two parts: Part I to explore the effect of high-salt diet on pregnant rats and the changes in inflammation and neurotransmitters in their male offspring PVN; Part II to reveal the influence on their offspring of bilateral PVN infusion of c-Src inhibitor dasatinib (DAS) in pregnant rats fed a high-salt diet. Maternal high-salt diet intake during copulation, pregnancy, and lactation impacted the offspring mean arterial pressure (MAP) and elevated the offspring PVN levels of p-Src, proinflammatory cytokines, and excitatory neurotransmitters. Bilateral PVN infusion of a c-Src inhibitor combined with maternal high-salt diets decreased MAP in the offspring. The infusion was also shown to suppress the Src-induced MAPK/NF-κB signaling pathway (p38 MAPK, JNK, Erk1/2), which attenuates inflammatory reactions. Finally, bilateral PVN infusion of the Src inhibitor in pregnant rat with high-salt diets improved the levels of inhibitory neurotransmitters in offspring PVN, which restored the excitatory-inhibitory neurotransmitter balance in male offspring. High-salt diets increase sympathetic activity and blood pressure in adult offspring, probably by activating the c-Src/MAPKs/NF-κB signaling pathway-induced inflammation. Moreover, NF-κB disrupts the downstream excitatory-inhibitory neurotransmitter balance in the PVN of male offspring.



中文翻译:


抑制母体 c-Src 通过抑制室旁核炎症和神经递质改善雄性后代高血压



母亲长期食盐会诱发子代高血压。大量研究还表明,高盐饮食会导致炎症和室旁核(PVN)神经递质失衡,从而导致血压和交感神经活动升高。本研究旨在探讨母亲盐摄入是否通过增加后代室旁核的炎症和神经递质平衡而诱发男性后代高血压。本研究包括两部分:第一部分探讨高盐饮食对妊娠大鼠的影响及其雄性子代PVN炎症和神经递质的变化;第二部分揭示高盐饮食妊娠大鼠双侧PVN输注c-Src抑制剂达沙替尼(DAS)对其后代的影响。母亲在交配、怀孕和哺乳期间摄入高盐饮食会影响后代平均动脉压 (MAP),并升高后代 PVN 的 p-Src、促炎细胞因子和兴奋性神经递质水平。双侧 PVN 输注 c-Src 抑制剂与母体高盐饮食相结合可降低后代的 MAP。该输注还被证明可以抑制 Src 诱导的 MAPK/NF-κB 信号通路(p38 MAPK、JNK、Erk1/2),从而减轻炎症反应。最后,高盐饮食的妊娠大鼠双侧 PVN 输注 Src 抑制剂提高了后代 PVN 的抑制性神经递质水平,从而恢复了雄性后代的兴奋性 - 抑制性神经递质平衡。高盐饮食可能通过激活 c-Src/MAPKs/NF-κB 信号通路诱导的炎症来增加成年后代的交感神经活动和血压。 此外,NF-κB 会破坏雄性后代 PVN 下游的兴奋性-抑制性神经递质平衡。

更新日期:2021-07-16
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