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母体高血糖会改变新生大鼠肺细胞外基质信号通路。

Maternal hyperglycemia modifies extracellular matrix signaling pathways in neonatal rat lung.

机构信息

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. anviar @ utu.fi

出版信息

Neonatology. 2010;98(4):387-96. doi: 10.1159/000317010. Epub 2010 Nov 4.

DOI:10.1159/000317010
PMID:21051908
Abstract

BACKGROUND

Maternal diabetes is associated with numerous adverse effects in fetal and neonatal organs, including the lungs.

OBJECTIVE

To investigate the effects of intrauterine hyperglycemia on neonatal lung biological signaling, we performed a microarray analysis in the lungs of four 14-day-old rat pups born to a hyperglycemic dam and in four age mate control pup lungs.

METHODS

Total RNA was isolated and cDNA was hybridized to the Illumina Sentrix® RatRef-12 BeadChip. A total of 22,000 genes were analyzed for expression profiles and functional gene clustering. Ten selected genes differentially expressed in microarray were additionally analyzed by the real-time polymerase chain reaction.

RESULTS

Two hundred twenty-seven genes were differentially expressed in neonatal rat lungs exposed to intrauterine hyperglycemia when compared to normoglycemic controls (fold change > 1.2, p < 0.001). Functional clustering analysis revealed increased expression in signaling pathways involved with extracellular matrix regulation. The most significantly downregulated functions were cell proliferation, extracellular region, cell adhesion and reactive oxygen species metabolism.

CONCLUSION

We found significant hyperglycemia-induced gene expression alterations in neonatal rat pulmonary tissue which may interfere with lung growth and biological signaling pathways.

摘要

背景

母体糖尿病与胎儿和新生儿器官的许多不良影响有关,包括肺部。

目的

为了研究宫内高血糖对新生儿肺生物学信号的影响,我们对 4 只 14 天大的来自高血糖母鼠的幼鼠肺和 4 只同龄对照幼鼠肺进行了微阵列分析。

方法

分离总 RNA,并将 cDNA 杂交到 Illumina Sentrix® RatRef-12 BeadChip 上。对 22,000 个基因进行了表达谱和功能基因聚类分析。通过实时聚合酶链反应对微阵列中差异表达的 10 个选定基因进行了额外分析。

结果

与正常血糖对照组相比,暴露于宫内高血糖的新生大鼠肺中有 227 个基因表达差异(倍数变化> 1.2,p < 0.001)。功能聚类分析显示,参与细胞外基质调节的信号通路表达增加。下调最明显的功能是细胞增殖、细胞外区域、细胞黏附和活性氧代谢。

结论

我们发现新生大鼠肺组织中存在显著的高血糖诱导的基因表达改变,这可能干扰肺生长和生物学信号通路。

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