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子痫前期的母体减少子宫胎盘灌注模型可诱导大鼠后代出现性别二态代谢反应。

The maternal reduced uteroplacental perfusion model of preeclampsia induces sexually dimorphic metabolic responses in rat offspring.

机构信息

Cellular and Molecular Research Center, Department of Anatomical Sciences, Birjand University of Medical Sciences, Birjand, Iran.

Department of Pathology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

Biol Sex Differ. 2022 Sep 15;13(1):48. doi: 10.1186/s13293-022-00458-8.

Abstract

BACKGROUND

Offspring born to preeclamptic mothers are prone to obesity, diabetes and hypertension in later life, but still, studies investigating the underlying mechanism are limited. Here, we aimed to investigate the impact of the reduced uteroplacental perfusion (RUPP) rat preeclampsia model on offspring metabolic outcomes.

METHODS

Timed pregnant Wistar rats underwent RUPP or sham surgeries on day 14 of gestation. Glucometabolic parameters were evaluated on postnatal days (PND), 14 (childhood), and 60 (young adult). In addition, intraperitoneal glucose tolerance test (IPGTT), homeostatic model assessment of insulin resistance (HOMA-IR), immunohistochemical staining for insulin in pancreatic islets, arterial blood pressure and 24-h urine protein (24hUP) excretion were performed at PND60.

RESULTS

Male, but not female, young adult rats (PND60) of RUPP dams exhibited an impaired IPGTT, decreased circulatory insulin and weakened pancreatic insulin immunoreactivity. Compared to the male offspring of the sham group, the body mass of male RUPP offspring significantly caught up after PND42, but it was not sex-specific. RUPP pups also exhibited upregulations in glucagon (only males) and ghrelin (both sexes with a more significant increase in males) during PND14-PND60. However, in sham offspring (both sexes), glucagon levels were downregulated and ghrelin levels unchanged during PND14-PND60. The blood pressure, HOMA-IR and 24hUP values did not alter in RUPP pups.

CONCLUSIONS

The overall results suggest that maternal RUPP has negative and sex-specific impacts on insulin, glucagon and ghrelin regulations in offspring and that, as young adults, male RUPP rats may be more prone to develop obesity and diabetes.

摘要

背景

子痫前期母亲所生的后代在以后的生活中容易肥胖、患糖尿病和高血压,但仍有研究对潜在的发病机制进行调查。在这里,我们旨在研究减少胎盘灌注(RUPP)大鼠子痫前期模型对后代代谢结果的影响。

方法

妊娠第 14 天,对 Wistar 大鼠进行 RUPP 或假手术。在产后第 14 天(儿童期)和第 60 天(青年期)评估葡萄糖代谢参数。此外,在产后第 60 天进行腹腔内葡萄糖耐量试验(IPGTT)、稳态模型评估胰岛素抵抗(HOMA-IR)、胰岛胰岛素免疫组织化学染色、动脉血压和 24 小时尿蛋白(24hUP)排泄。

结果

RUPP 母鼠的雄性而非雌性青年期(产后第 60 天)大鼠的 IPGTT 受损,循环胰岛素减少,胰岛胰岛素免疫反应减弱。与假手术组雄性后代相比,RUPP 后代的体重在产后第 42 天显著增加,但没有性别特异性。RUPP 幼仔在产后第 14 天至第 60 天期间还表现出胰高血糖素(仅雄性)和胃饥饿素(雌雄均上调,雄性更为明显)的上调。然而,在假手术后代(雌雄)中,胰高血糖素水平在产后第 14 天至第 60 天期间下调,而胃饥饿素水平不变。RUPP 幼仔的血压、HOMA-IR 和 24hUP 值没有改变。

结论

总体结果表明,母体 RUPP 对子代胰岛素、胰高血糖素和胃饥饿素的调节具有负面和性别特异性影响,并且作为青年期大鼠,雄性 RUPP 大鼠可能更容易发生肥胖和糖尿病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3867/9479437/cf5473fc5a57/13293_2022_458_Fig1_HTML.jpg

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