H2S 供体 GYY4137 可减轻 sFlt-1 诱导的妊娠大鼠高血压和血管功能障碍

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Pankaj Yadav, Jay S Mishra, Mason William Hurt, Dong-Bao Chen, Sathish Kumar
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引用次数: 0

摘要

背景:妊娠高血压通常与可溶性 Fms 相关受体酪氨酸激酶 1(sFlt-1)的升高有关,对母体和胎儿的健康构成重大风险。硫化氢(H2S)是一种气体递质,在高血压动物和人类中具有降低血压的作用。然而,它在妊娠诱发高血压中的作用仍不清楚:本研究旨在探讨缓释 H2S 供体 GYY4137 对 sFlt-1 诱导的妊娠大鼠高血压的影响,并研究其潜在机制:从妊娠第 12 天到第 20 天,给妊娠大鼠静脉注射 sFlt-1(6 μg/kg/天,静脉注射)或药物。其中一组从妊娠期第 16 天到第 20 天接受 GYY4137(一种 H2S 供体,50 毫克/千克/天,皮下注射)。对血清 H2S 水平、平均动脉血压(CODA 尾袖)、子宫动脉血流(超声波检查)、血管对血管加压素的反应性和内皮依赖性松弛(肌电图)、子宫动脉中内皮一氧化氮合酶(eNOS)蛋白表达(Western 印迹)进行了评估。此外,还测量了母体的体重增加以及胎儿和胎盘的重量:结果:sFlt-1升高会降低母体体重增加和血清H2S水平。GYY4137 治疗可恢复 sFlt-1 母鼠的体重增加和 H2S 水平。sFlt-1 会增加妊娠大鼠的平均动脉压并降低子宫动脉血流。然而,用 GYY4137 治疗可使 sFlt-1 母鼠的血压恢复正常并恢复子宫血流量。sFlt-1 母鼠对苯肾上腺素的血管收缩作用增强,而 GYY4137 可显著缓解血管的过度收缩。值得注意的是,sFlt-1 会损害内皮依赖性松弛,而 GYY4137 可通过上调 eNOS 蛋白水平和增强子宫动脉的血管舒张来减轻这种损害。结论:sFlt-1 介导的高血压与 H2S 水平下降有关。结论:sFlt-1 介导的高血压与 H2S 水平下降有关。用供体 GYY4137 补充 H2S 可缓解高血压,改善血管功能和胎儿生长结果。这表明调节 H2S 可为控制妊娠高血压和对胎儿的不良影响提供一种新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
H2S donor GYY4137 mitigates sFlt-1-induced hypertension and vascular dysfunction in pregnant rats†.

Gestational hypertension, often associated with elevated soluble Fms-related receptor tyrosine kinase 1 (sFlt-1), poses significant risks to both maternal and fetal health. Hydrogen sulfide (H2S), a gasotransmitter, has demonstrated blood pressure-lowering effects in hypertensive animals and humans. However, its role in pregnancy-induced hypertension remains unclear. This study investigated the impact of GYY4137, a slow-release H2S donor, on sFlt-1-induced hypertension in pregnant rats . Pregnant rats were administered sFlt-1 (6 μg/kg/day, intravenously) or vehicle from gestation day (GD) 12-20. A subset of these groups received GYY4137 ( 50 mg/kg/day, intraperitoneal) from GD 16-20. Serum H2S levels, mean arterial blood pressure, uterine artery blood flow, and vascular reactivity were assessed. Elevated sFlt-1 reduced both maternal weight gain and serum H2S levels. GYY4137 treatment restored both weight gain and H2S levels in sFlt-1 dams. sFlt-1 increased mean arterial pressure and decreased uterine artery blood flow in pregnant rats. However, treatment with GYY4137 normalized blood pressure and restored uterine blood flow in sFlt-1 dams. sFlt-1 dams exhibited heightened vasoconstriction to phenylephrine and GYY4137 significantly mitigated the exaggerated vascular contraction. Notably, sFlt-1 impaired endothelium-dependent relaxation, while GYY4137 attenuated this impairment by upregulating eNOS protein levels and enhancing vasorelaxation in uterine arteries. GYY4137 mitigated sFlt-1-induced fetal growth restriction. In conclusion, sFlt-1 mediated hypertension is associated with decreased H2S levels. Replenishing H2S with the donor GYY4137 mitigates hypertension and improves vascular function and fetal growth outcomes. This suggests modulation of H2S could offer a novel therapeutic strategy for managing gestational hypertension and adverse fetal effects.

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CiteScore
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