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子痫前期女性体内晚期糖基化终末产物的高血浆水平与代谢改变及胰岛素抵抗相关。

High Plasmatic Levels of Advanced Glycation End Products are Associated with Metabolic Alterations and Insulin Resistance in Preeclamptic Women.

作者信息

García-Gómez Elizabeth, Bobadilla-Bravo Mariana, Díaz-Díaz Eulises, Vázquez-Martínez Edgar Ricardo, Nava-Salazar Sonia, Torres-Ramos Yessica, García-Romero Carmen Selene, Camacho-Arroyo Ignacio, Cerbón Marco

机构信息

Unidad de Investigacion en Reproduccion Humana, Consejo Nacional de Ciencia y Tecnologia (CONACyT)- Instituto Nacional de Perinatologia, Mexico.

Unidad de Investigacion en Reproduccion Humana, Instituto Nacional de Perinatologia-Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Mexico.

出版信息

Curr Mol Med. 2020;20(9):751-759. doi: 10.2174/1566524020666200220141414.

Abstract

AIMS

The purpose of this study was to investigate the association between plasmatic levels of advanced end glycation products (AGEs) and the metabolic profile in subjects diagnosed with preeclampsia, due to the known relation of these molecules with oxidative stress and inflammation, which in turn are related with PE pathogenesis.

BACKGROUND

It has been reported that increased levels of AGEs are observed in patients with preeclampsia as compared with healthy pregnant subjects, which was mainly associated with oxidative stress and inflammation. Besides, in women with preeclampsia, there are metabolic changes such as hyperinsulinemia, glucose intolerance, dyslipidemia, among others, that are associated with an exacerbated insulin resistance. Additionally, some parameters indicate the alteration of hepatic function, such as increased levels of liver enzymes. However, the relationship of levels of AGEs with altered lipidic, hepatic, and glucose metabolism parameters in preeclampsia has not been evaluated.

OBJECTIVE

To investigate the association between plasmatic levels of AGEs and hepatic, lipid, and metabolic profiles in women diagnosed with preeclampsia.

METHODS

Plasma levels of AGEs were determined by a competitive enzyme-linked immunosorbent assay (ELISA) in 15 patients diagnosed with preeclampsia and 28 normoevolutive pregnant subjects (control group). Hepatic (serum creatinine, gammaglutamyl transpeptidase, aspartate transaminase, alanine transaminase, uric acid, and lactate dehydrogenase), lipid (apolipoprotein A, apolipoprotein B, total cholesterol, triglycerides, low-density lipoproteins, and high-density lipoproteins), and metabolic variables (glucose, insulin, and insulin resistance) were assessed.

RESULTS

Plasmatic levels of AGEs were significantly higher in patients with preeclampsia as compared with the control. A positive correlation between circulating levels of AGEs and gamma-glutamyl transpeptidase, uric acid, glucose, insulin, and HOMA-IR levels was found in patients with preeclampsia. In conclusion, circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, variables of hepatic and metabolic profile, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance.

CONCLUSIONS

Circulating levels of AGEs were higher in patients with preeclampsia than those observed in healthy pregnant subjects. Besides, hepatic and metabolic profiles, particularly those related to insulin resistance, were higher in preeclampsia as compared with healthy pregnant subjects. Interestingly, there is a positive correlation between AGEs levels and insulin resistance, suggesting that excessive glycation and an impaired metabolic profile contribute to the physiopathology of preeclampsia.

摘要

目的

本研究旨在探讨晚期糖基化终末产物(AGEs)血浆水平与子痫前期患者代谢谱之间的关联,因为已知这些分子与氧化应激和炎症相关,而氧化应激和炎症又与子痫前期的发病机制有关。

背景

据报道,与健康孕妇相比,子痫前期患者体内AGEs水平升高,这主要与氧化应激和炎症有关。此外,子痫前期女性存在代谢变化,如高胰岛素血症、葡萄糖不耐受、血脂异常等,这些都与胰岛素抵抗加剧有关。此外,一些参数表明肝功能发生改变,如肝酶水平升高。然而,子痫前期患者中AGEs水平与脂质、肝脏和葡萄糖代谢参数改变之间的关系尚未得到评估。

目的

研究子痫前期女性血浆AGEs水平与肝脏、脂质和代谢谱之间的关联。

方法

采用竞争性酶联免疫吸附测定(ELISA)法测定15例子痫前期患者和28例正常妊娠孕妇(对照组)的血浆AGEs水平。评估肝脏(血清肌酐、γ-谷氨酰转肽酶、天冬氨酸转氨酶、丙氨酸转氨酶、尿酸和乳酸脱氢酶)、脂质(载脂蛋白A、载脂蛋白B、总胆固醇、甘油三酯、低密度脂蛋白和高密度脂蛋白)和代谢变量(葡萄糖、胰岛素和胰岛素抵抗)。

结果

与对照组相比,子痫前期患者的血浆AGEs水平显著更高。子痫前期患者中,AGEs循环水平与γ-谷氨酰转肽酶、尿酸、葡萄糖、胰岛素和HOMA-IR水平呈正相关。总之,子痫前期患者的AGEs循环水平高于健康孕妇。此外,与健康孕妇相比,子痫前期患者的肝脏和代谢谱变量,特别是与胰岛素抵抗相关的变量更高。有趣的是,AGEs水平与胰岛素抵抗之间存在正相关。

结论

子痫前期患者的AGEs循环水平高于健康孕妇。此外,与健康孕妇相比,子痫前期患者的肝脏和代谢谱,特别是与胰岛素抵抗相关的更高。有趣的是,AGEs水平与胰岛素抵抗之间存在正相关,这表明过度糖基化和代谢谱受损有助于子痫前期的病理生理过程。

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