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子痫前期的胎盘表达谱分析:血红蛋白的局部过度产生可能驱动病理变化。

Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes.

作者信息

Centlow Magnus, Carninci Piero, Nemeth Krisztian, Mezey Eva, Brownstein Michael, Hansson Stefan R

机构信息

Department of Obstetrics and Gynecology, Lund University, Lund, Sweden.

出版信息

Fertil Steril. 2008 Nov;90(5):1834-43. doi: 10.1016/j.fertnstert.2007.09.030. Epub 2007 Dec 31.

DOI:10.1016/j.fertnstert.2007.09.030
PMID:18166190
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2628488/
Abstract

OBJECTIVE

To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiling of preeclampsia (PE) and high risk pregnancies.

DESIGN

Prospective study.

SETTING

University women's clinic and academic research laboratory.

PATIENT(S): Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited.

INTERVENTION(S): Placenta and placenta bed biopsies were collected after delivery.

MAIN OUTCOME MEASURE(S): Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time polymerase chain reaction (PCR) and histologically using in situ hybridization and immunohistochemistry.

RESULT(S): Thirty genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative real-time PCR. Hemoglobin alpha2 and gamma transcripts were significantly overexpressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin chains.

CONCLUSION(S): We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins that cause endothelial damage and inflammation.

摘要

目的

构建一个富含子痫前期胎盘cDNA的文库,用于打印到微阵列上,以对子痫前期(PE)和高危妊娠进行胎盘分析。

设计

前瞻性研究。

地点

大学妇女诊所和学术研究实验室。

患者

招募了10例PE患者、5例伴有双侧切迹的PE患者、5例无PE的双侧切迹患者和15例血压正常的患者。

干预措施

分娩后收集胎盘和胎盘床活检组织。

主要观察指标

构建PE转录本的消减文库,并用这些文库中的cDNA制作PE特异性cDNA阵列。结果通过实时聚合酶链反应(PCR)进行定量验证,通过原位杂交和免疫组织化学进行组织学验证。

结果

在至少一组比较中,有30个基因发生了显著改变。使用定量实时PCR证实了两个候选基因的差异。血红蛋白α2和γ转录本在PE胎盘中显著过度表达。胎盘和胎盘血管中的散在细胞显示表达编码这些血红蛋白链的基因。

结论

我们证明了PE胎盘中血红蛋白产生增加。血红蛋白可能释放到胎盘血管腔中。游离血红素和血红蛋白是导致内皮损伤和炎症的强效毒素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/8629df902736/nihms-77922-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/81dbae3c9cc7/nihms-77922-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/54d3902db761/nihms-77922-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/97d55ac8db70/nihms-77922-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/8629df902736/nihms-77922-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/81dbae3c9cc7/nihms-77922-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/54d3902db761/nihms-77922-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/97d55ac8db70/nihms-77922-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6130/2628488/8629df902736/nihms-77922-f0004.jpg

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