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在妊娠期和哺乳期用抗氧化剂替米泊芬治疗自发性高血压大鼠可降低血压并减少氧化应激。

Treatment of spontaneously hypertensive rats during pregnancy and lactation with the antioxidant tempol lowers blood pressure and reduces oxidative stress.

机构信息

Department of Experimental Animals, Interdisciplinary Center for Science Research, Head Office for Research and Academic Information, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.

Department of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Head Office for Research and Academic Information, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.

出版信息

Exp Anim. 2024 May 3;73(2):136-144. doi: 10.1538/expanim.23-0069. Epub 2023 Oct 12.

Abstract

Genetic and environmental factors interact in a complex manner in the pathogenesis of essential hypertension in humans. Oxidative stress is considered one of the more important environmental factors. We used the spontaneously hypertensive rat (SHR) model to test whether continuous feeding with the antioxidant tempol reduces maternal oxidative stress during pregnancy and potentially contributes to the prevention of cardiovascular disease onset. Pregnant female rats were divided into control and tempol-treated groups. Tempol was continuously administered in drinking water. The administration period lasted approximately 40 days, from the confirmation of a vaginal plug until birth of the pups and their subsequent weaning. The blood pressure (BP) of each adult female was measured three times during pregnancy and post parturition. Milk was collected three times from nursing mother rats in the immediate postpartum period. Markers of oxidative stress were measured: 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels in milk during the experimental period and 8-OHdG and corticosterone levels in urine of adult and neonatal rats. The urinary level of 8-OHdG in the tempol-treated group was significantly lower than that in the control group. Corticosterone levels were significantly lower in urine of neonatal rats from the tempol-treated group compared with the levels of the control group. The levels of total antioxidant in milk were significantly greater in the tempol-treated group than in the control group. This study demonstrated that continuous administration of tempol to pregnant SHRs reduced maternal oxidative stress and contributed to reduced oxidative stress in neonatal rats.

摘要

遗传和环境因素在人类原发性高血压的发病机制中以复杂的方式相互作用。氧化应激被认为是一个更重要的环境因素。我们使用自发性高血压大鼠(SHR)模型来测试怀孕期间连续给予抗氧化剂替米泊酚是否能减轻母体的氧化应激,并可能有助于预防心血管疾病的发生。将怀孕的雌性大鼠分为对照组和替米泊酚处理组。替米泊酚连续添加在饮用水中。给药期持续约 40 天,从阴道塞的确认到幼崽的出生及其随后的断奶。在怀孕期间和分娩后,每位成年雌性大鼠的血压(BP)测量了三次。在产后即刻从哺乳母鼠中收集了三次牛奶。测量了氧化应激的标志物:实验期间牛奶中的 8-羟基-2'-脱氧鸟苷(8-OHdG)水平以及成年和新生大鼠尿液中的 8-OHdG 和皮质酮水平。替米泊酚处理组大鼠的尿液 8-OHdG 水平明显低于对照组。与对照组相比,替米泊酚处理组新生大鼠尿液中的皮质酮水平明显较低。牛奶中的总抗氧化剂水平在替米泊酚处理组明显高于对照组。这项研究表明,连续给予替米泊酚给怀孕的 SHR 可减轻母体的氧化应激,并有助于降低新生大鼠的氧化应激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b64/11091351/6d3d527720cc/expanim-73-136-g001.jpg

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