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正常孕期女性循环中羧甲基赖氨酸、晚期糖基化终末产物可溶性受体(sRAGE)及炎症标志物水平的变化。

Changes in circulating levels of carboxymethyllysine, soluble receptor for advanced glycation end products (sRAGE), and inflammation markers in women during normal pregnancy.

作者信息

Quintanilla-García Claudia V, Uribarri Jaime, Fajardo-Araujo Martha Eugenia, Barrientos-Romero José Juan, Romero-Gutiérrez Gustavo, Reynaga-Ornelas Ma Guadalupe, Garay-Sevilla Ma Eugenia

机构信息

Department of Medical Sciences, Division of Health Sciences, Guanajuato, Mexico.

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

J Matern Fetal Neonatal Med. 2019 Dec;32(24):4102-4107. doi: 10.1080/14767058.2018.1481948. Epub 2018 Jun 25.

Abstract

To determine the circulating levels of insulin, Nε-carboxymethyllysine (CML), soluble receptor for advanced glycation end products (sRAGE), and markers of inflammation and oxidative stress (OS) in maternal and umbilical cord blood in a cohort of healthy women with normal pregnancy. We conducted an observational longitudinal study in a group of women ( = 31; age range 18-39 years) with healthy pregnancy starting at 30 weeks of gestation and finishing at the time of delivery. We collected weight and height in the participants and their neonates and calculated body mass index (BMI). Blood from each patient was collected at 30th week of pregnancy and at delivery when a sample of cord blood was also obtained. Glucose, lipid profile, CML, sRAGE, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), highly sensitivity C-reactive protein (hsPCR), and insulin were determined. The study was approved by the University of Guanajuato Institutional Ethics Committee. All pregnancies reached term (mean gestational time 38.9 ± 0.83 weeks) and there were no maternal complications. Mean age was 27.6 years. Lipid profile values were higher in the group compared with our values in nonpregnant women. During pregnancy, levels of insulin increased ( < .0006), CML ( < .0001) and sRAGE ( < .01) decreased, levels of MDA did not change, while those of TNF-α and hsPCR tended to increase. In the neonates, we found lower levels of CML ( < .003), hsPCR ( < .004), and insulin ( < .004) and higher levels of sRAGE ( < .013) and TNF-α ( < .022) compared to their mothers at delivery. In the total group, we found association of CML of the mother at baseline with the CML ( < .0006) and MDA ( < .002) in neonates, while maternal sRAGE at the end of pregnancy was associated with CML ( < .004) of their neonates. Our study confirms that normal pregnancy is accompanied by insulin resistance (IR) and significant increase in lipid profile, and demonstrates that circulating levels of CML and sRAGE decreased significantly at the end of pregnancy. The lack of association between the course of insulin levels and those of CML probably results from the predominant role of placental factors in the pathogenesis of IR in pregnancy. sRAGE levels in the neonates are markedly increased compared to their mothers suggesting a placental origin of this compound which may have a protective effect on the fetus since sRAGE restricts Advanced glycation end product (AGE) effects and may exert anti-inflammatory effects.

摘要

为了测定一组正常妊娠的健康女性母血和脐血中胰岛素、Nε-羧甲基赖氨酸(CML)、晚期糖基化终产物可溶性受体(sRAGE)以及炎症和氧化应激(OS)标志物的循环水平。我们对一组妊娠健康的女性(n = 31;年龄范围18 - 39岁)进行了一项观察性纵向研究,研究从妊娠30周开始,至分娩时结束。我们收集了参与者及其新生儿的体重和身高,并计算了体重指数(BMI)。在妊娠第30周和分娩时采集每位患者的血液,同时采集脐血样本。测定了葡萄糖、血脂谱、CML、sRAGE、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、高敏C反应蛋白(hsPCR)和胰岛素。该研究获得了瓜纳华托大学机构伦理委员会的批准。所有妊娠均足月(平均妊娠时间38.9 ± 0.83周),且无母体并发症。平均年龄为27.6岁。与我们非妊娠女性的血脂谱值相比,该组血脂谱值更高。在妊娠期间,胰岛素水平升高(P < 0.0006),CML(P < 0.0001)和sRAGE(P < 0.01)水平降低,MDA水平未变化,而TNF-α和hsPCR水平有升高趋势。在新生儿中,我们发现与分娩时的母亲相比,CML(P < 0.003)、hsPCR(P < 0.004)和胰岛素(P < 0.004)水平较低,而sRAGE(P < 0.013)和TNF-α(P < 0.022)水平较高。在整个研究组中,我们发现母亲基线时的CML与新生儿的CML(P < 0.0006)和MDA(P < 0.002)相关,而妊娠末期母亲的sRAGE与新生儿的CML(P < 0.004)相关。我们的研究证实,正常妊娠伴有胰岛素抵抗(IR)和血脂谱显著升高,并表明妊娠末期CML和sRAGE的循环水平显著降低。胰岛素水平变化过程与CML水平变化之间缺乏关联,可能是由于胎盘因素在妊娠IR发病机制中起主要作用。与母亲相比,新生儿的sRAGE水平显著升高,提示该化合物可能来源于胎盘,由于sRAGE可限制晚期糖基化终产物(AGE)的作用并可能发挥抗炎作用,故可能对胎儿具有保护作用。

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