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PP014. 评估宫内生长受限和健康对照胎盘组织中完全氧化和最小氧化低密度脂蛋白的蓄积情况。

PP014. Estimating fully and minimal oxidized low density lipoprotein accumulation in placental tissue in intrauterine growth restriction and healthy controls.

作者信息

Pecks U, Caspers R, Sosnowsky K, Rath W, Huppertz B

机构信息

Department of Obstetrics and Gynecology, University Hospital of the RWTH Aachen, Aachen, Germany.

Department of Obstetrics and Gynecology, University Hospital of the RWTH Aachen, Aachen, Germany; Institute of Cell Biology, Histology, and Embryology, Medical Faculty, Graz, Austria.

出版信息

Pregnancy Hypertens. 2012 Jul;2(3):248. doi: 10.1016/j.preghy.2012.04.125. Epub 2012 Jun 13.

Abstract

INTRODUCTION

We recently demonstrated that maternal serum LDL- and fetal serum HDL-cholesterol concentration is significantly reduced in intrauterine growth restriction (IUGR) [1].

OBJECTIVES

We now hypothesized that increased oxidative stress in IUGR placenta leads to an accumulation of oxidized LDL (oxLDL) particles which then become trapped within the placenta subsequently leading to reduced availability of cholesterol for mother and fetus.

METHODS

Fully oxidized LDL (oxLDL) was determined via immunohistochemistry in placental paraffin sections of 18 women suffering from IUGR and 18 gestational age matched controls. Ten 'High Power Fields' were chosen randomly by the newCAST software and oxLDL expression was estimated via standardized methods by two independent and blinded observers. Minimal oxidatively modified LDL (MM-LDL) and non-modified Apolipoprotein B (ApoB) concentration was measured in full placental tissue lysates by ELISA. Values were correlated with maternal and fetal total cholesterol, LDL-, and HDL-cholesterol concentrations. Statistical examinations were carried out by Student's t-test and calculation of Pearson's correlation coefficient.

RESULTS

oxLDL was found predominantly to be in villous trophoblast and placental endothelium. OxLDL intensity tended to be increased in IUGR (Table 1). We found MM-LDL concentrations in whole placental tissue lysates to be highly correlated to placental ApoB concentration (r=0.93). Both parameters were non-significantly decreased in placenta of IUGR compared to controls (Table 1). Maternal serum LDL-C, and fetal serum LDL-C, TC, and HDL-C concentrations were significantly decreased in IUGR compared to controls (Table 2). OxLDL staining intensity was mildly negatively correlated to maternal LDL-C (r=-0.315) and much less to fetal HDL-C concentrations (r=-0.212). Placental ApoB and MM-LDL concentration were moderately positively correlated with fetal HDL-C concentrations (r=0.492 and r=0.447).

CONCLUSION

Conformational changes of the ApoB lipoprotein during the process of oxidation might lead to an accumulation of oxLDL particles in placental tissue of IUGR and reduced fetal cholesterol bioavailability as evidenced by a decrease in fetal serum cholesterol levels. However, our analysis lacks in sufficient power and further studies are underway focussing on that subject.

摘要

引言

我们最近证明,在宫内生长受限(IUGR)中,母体血清低密度脂蛋白(LDL)和胎儿血清高密度脂蛋白(HDL)胆固醇浓度显著降低[1]。

目的

我们现在假设,IUGR胎盘氧化应激增加导致氧化型LDL(oxLDL)颗粒积累,这些颗粒随后被困在胎盘内,从而导致母体和胎儿可利用的胆固醇减少。

方法

通过免疫组织化学法测定18例IUGR患者和18例孕周匹配的对照者胎盘石蜡切片中的完全氧化型LDL(oxLDL)。newCAST软件随机选择10个“高倍视野”,由两名独立且不知情的观察者通过标准化方法评估oxLDL表达。通过酶联免疫吸附测定法(ELISA)测量全胎盘组织裂解物中的最小氧化修饰LDL(MM-LDL)和未修饰的载脂蛋白B(ApoB)浓度。将这些值与母体和胎儿的总胆固醇、LDL和HDL胆固醇浓度进行相关性分析。采用学生t检验和计算皮尔逊相关系数进行统计学检验。

结果

oxLDL主要存在于绒毛滋养层和胎盘内皮细胞中。IUGR中oxLDL强度有增加趋势(表1)。我们发现全胎盘组织裂解物中的MM-LDL浓度与胎盘ApoB浓度高度相关(r = 0.93)。与对照组相比,IUGR胎盘的这两个参数均无显著降低(表1)。与对照组相比,IUGR中母体血清LDL-C、胎儿血清LDL-C、总胆固醇(TC)和HDL-C浓度显著降低(表2)。oxLDL染色强度与母体LDL-C呈轻度负相关(r = -0.315),与胎儿HDL-C浓度的相关性则小得多(r = -0.212)。胎盘ApoB和MM-LDL浓度与胎儿HDL-C浓度呈中度正相关(r = 0.492和r = 0.447)。

结论

氧化过程中ApoB脂蛋白的构象变化可能导致IUGR胎盘组织中oxLDL颗粒积累,以及胎儿胆固醇生物利用度降低,胎儿血清胆固醇水平下降证明了这一点。然而,我们的分析力度不足,目前正在针对该主题开展进一步研究。

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