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环境干扰使 Wistar 大鼠产前糖皮质激素编程实验复杂化。

Environmental disturbance confounds prenatal glucocorticoid programming experiments in Wistar rats.

机构信息

Anaesthetics Department, The Royal Marsden Hospital NHS Foundation Trust, London, UK.

出版信息

Lab Anim. 2010 Jul;44(3):199-205. doi: 10.1258/la.2009.009032. Epub 2010 Jan 13.

Abstract

Low birth weight in humans is predictive of hypertension in adult life, and while the mechanisms underlying this link remain unknown, fetal overexposure to glucocorticoids has been implicated. We have previously shown that prenatal dexamethasone (DEX) exposure in the rat lowers birth weight and programmes adult hypertension. This current study aimed to unravel the molecular nature of this hypertension. However, unknowingly, post hoc investigations revealed that our animals had been subjected to environmental noise stresses from an adjacent construction site, which were sufficient to confound our prenatal DEX-programming experiments. This perinatal stress successfully established low birth weight, hypercorticosteronaemia, insulin resistance, hypertension and hypothalamic-pituitary-adrenal axis dysfunction in vehicle (VEH)-treated offspring, such that the typical distinctions between both treatment groups were ameliorated. The lack of an additional effect on DEX-treated offspring is suggestive of a maximal effect of perinatal stress and glucocorticoids, serving to prevent against the potentially detrimental effects of sustained glucocorticoid hyper-exposure. Finally, this paper serves to inform researchers of the potential detrimental effects of neighbouring construction sites to their experiments.

摘要

人类的低出生体重与成年期高血压有关,尽管这种联系的机制尚不清楚,但胎儿过度暴露于糖皮质激素已被牵连其中。我们之前的研究表明,在大鼠中产前给予地塞米松(DEX)暴露会降低出生体重并导致成年期高血压。本研究旨在揭示这种高血压的分子本质。然而,在事后调查中我们无意中发现,我们的动物受到了来自附近建筑工地的环境噪声压力,这足以混淆我们的产前 DEX 编程实验。这种围产期应激成功地在接受载体(VEH)治疗的后代中建立了低出生体重、高皮质酮血症、胰岛素抵抗、高血压和下丘脑-垂体-肾上腺轴功能障碍,使得两个治疗组之间的典型差异得到了改善。在 DEX 处理的后代中没有额外的影响表明围产期应激和糖皮质激素的作用达到了最大,这有助于防止持续的糖皮质激素过度暴露的潜在有害影响。最后,本文旨在提醒研究人员附近建筑工地对其实验的潜在有害影响。

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