Periconceptional 1,3-butanediol supplementation suppresses the superimposed preeclampsia-like phenotype in the Dahl salt-sensitive rat
Periconceptional 1,3-butanediol supplementation suppresses the superimposed preeclampsia-like phenotype in the Dahl salt-sensitive rat
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DOI：
10.1152/ajpheart.00060.2021
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发表时间：
2022-02-01
影响因子：
4.8
通讯作者：
Sasser, Jennifer M.
中科院分区：
文献类型：
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作者：
Ishimwe, Jeanne A.;Baker, Melanie B.;Sasser, Jennifer M.
先兆子痫是一种妊娠期高血压疾病，除了控制症状和胎儿及胎盘的分娩外，没有其他治疗方法。慢性高血压会增加发生先兆子痫的风险。先前的报告表明，1，3-丁二醇减轻啮齿动物的高血压;然而，尚未研究1，3-丁二醇预防先兆子痫的治疗潜力。本研究验证了以下假设：在妊娠前和整个胎盘形成期通过1，3-丁二醇降低高血压可预防雌性Dahl盐敏感（SS/Jr）大鼠发生先兆子痫。将雌性Dahl SS/Jr大鼠分为两组：1，3-丁二醇处理组（20%通过饮用水）和对照组（自由饮水）。两组均维持低盐啮齿动物饲料（Teklad 7034，0.3% NaCl; n = 8/组）。动物用1，3-丁二醇处理7周（基线），交配，并处理至妊娠第12天。1，3-丁二醇治疗增加了血浆β-羟基丁酸（1，3-丁二醇的代谢产物），这与妊娠后期母体体重呈负相关。治疗组在基线、妊娠早期和中期的平均动脉压较低，但在治疗结束后的妊娠晚期没有观察到差异。子宫动脉阻力指数（UARI）在处理的母鼠降低。未观察到不良胎仔影响，幼仔体重或身长无差异。给药母鼠的胎盘血管内皮生长因子水平降低，胎盘基底区厚度降低，迷路区厚度增加。这些发现支持了通过1，3-丁二醇的生理性酮症作为一种潜在的治疗方法来管理慢性高血压的治疗作用，从而预防和减轻与先兆子痫相关的不良妊娠结局。新&值得注意的是生酮饮食或增加对羟基丁酸水平可以降低高血压，但1，3-丁二醇，一种13-羟基丁酸前体，治疗先兆子痫的潜力尚不清楚。我们假设，通过1，3-丁二醇降低妊娠前和妊娠期间的高血压可预防达尔盐敏感大鼠的先兆子痫。1，3-丁二酮显著降低血压，改善子宫动脉阻力，未观察到不良胎儿影响。通过1，3-丁二醇的生理性酮症可能是管理高血压和减轻不良妊娠结局的潜在治疗方法。
Preeclampsia is a hypertensive pregnancy disorder with no treatment beyond management of symptoms and delivery of the fetus and placenta. Chronic hypertension increases the risk of developing superimposed preeclampsia. Previous reports showed that 1,3-butanediol attenuates hypertension in rodents; however, the therapeutic potential of 1,3-butanediol for the prevention of preeclampsia has not been investigated. This study tested the hypothesis that attenuating hypertension before pregnancy and through the placentation period via 1,3-butanediol prevents the onset of preeclampsia in female Dahl salt-sensitive (SS/Jr) rats. Female Dahl SS/Jr rats were divided into two groups: 1,3-butanediol treated (20% via drinking water) and control (ad libitum water). Both groups were maintained on low-salt rodent chow (Teklad 7034, 0.3% NaCl; n = 8/group). Animals were treated with 1,3-butanediol for 7 wk (baseline), mated, and treated through day 12 of pregnancy. 1,3-Butanediol treatment increased plasma beta-hydroxybutyrate (metabolite of 1,3-butanediol) that negatively correlated with maternal body weight in late pregnancy. Mean arterial pressure was lower in the treated group at baseline, early, and mid pregnancy, but no difference was observed in late pregnancy after treatment ended. Uterine artery resistance index (UARI) was reduced in the treated dams. No adverse fetal effects were observed, and there were no differences in pup weight or length. Placentas from treated dams had decreased vascular endothelial growth factor levels as well as decreased placental basal zone thickness and increased labyrinth zone thickness. These findings support the therapeutic role of physiological ketosis via 1,3-butanediol as a potential therapeutic approach for managing chronic hypertension, thereby preventing and mitigating adverse pregnancy outcomes associated with preeclampsia.NEW & NOTEWORTHY A ketogenic diet or increased p-hydroxybutyrate levels can reduce hypertension, but the potential of 1,3-butanediol, a 13-hydroxybutyrate precursor, for treatment of preeclampsia is unknown. We hypothesized that attenuating hypertension before and during pregnancy via 1,3-butanediol prevents preeclampsia in Dahl Salt-sensitive rats. 1,3-Butanediol significantly lowered blood pressure and improved uterine artery resistance with no observable adverse fetal effects. Physiological ketosis via 1,3-butanediol may be a potential therapeutic approach for managing hypertension and mitigating adverse pregnancy outcomes.