Institute of Pediatrics, Nanjing Medical University, Nanjing, 210029, China.
J Mol Neurosci. 2013 Nov;51(3):941-9. doi: 10.1007/s12031-013-9958-y. Epub 2013 Jan 25.
Over the recent decades, with numbers of premature infants being cured, clinical diseases on brain damage like periventricular leukomalacia (PVL) have become much more common. Meanwhile, since the discovery of first miRNA lin-4, an increasing number of important studies about this small RNA have been performed not only in the normal organ development but also in the pathogenic mechanism of diseases. However, throughout the past several years, there have been rare miRNA researches discussing the connection between the PVL and miRNA. In view of this situation, we constructed an animal model of PVL induced by lipopolysaccharide (LPS) and performed a miRNA microarray which was repeated three times to profile the expression of microRNAs (miRNAs) between two groups (PVL group versus control group). Then, miRNAs with notable fold changes (fold change >1.5) were found; some of them were further validated by real-time PCR. As a result, 104 differentially expressed miRNAs were identified using the microarray, including 64 upregulated and 40 downregulated miRNAs. Then, five miRNAs of them were selected, characterized by consistent trend in expression in all three microarrays. Among these five miRNAs (miRNA-451, miRNA-200b, miRNA-29a, miRNA-21, and miRNA-138), we subsequently selected miRNA-451 and miRNA-200b for real-time PCR because they possess the highest fold changes. Finally, the results of PCR are basically in accord with the microarray. We guess these new identified miRNAs may play an important role in the pathogenesis of PVL and may provide certain pathophysiological basis for the future research of related diseases in preterm infants.
在最近几十年,随着早产儿数量的增加,脑损伤相关的临床疾病(如脑室周围白质软化症,PVL)变得更加常见。同时,自第一个 microRNA lin-4 被发现以来,人们对这种小 RNA 的研究越来越多,不仅涉及正常器官发育,还涉及疾病的发病机制。然而,在过去的几年中,很少有 miRNA 研究探讨 PVL 与 miRNA 之间的联系。鉴于这种情况,我们构建了 LPS 诱导的 PVL 动物模型,并进行了 miRNA 微阵列分析,该分析重复了三次,以分析两组(PVL 组与对照组)之间 microRNA(miRNA)的表达谱。然后,我们发现了具有显著倍数变化(倍数变化>1.5)的 miRNA,其中一些通过实时 PCR 进一步验证。结果,微阵列鉴定出 104 个差异表达的 miRNA,包括 64 个上调和 40 个下调的 miRNA。然后,选择了其中的 5 个 miRNA,它们在所有三个微阵列中的表达趋势一致。在这 5 个 miRNA(miRNA-451、miRNA-200b、miRNA-29a、miRNA-21 和 miRNA-138)中,我们随后选择 miRNA-451 和 miRNA-200b 进行实时 PCR 分析,因为它们具有最高的倍数变化。最后,PCR 结果与微阵列基本一致。我们推测这些新鉴定的 miRNA 可能在 PVL 的发病机制中发挥重要作用,并为未来早产儿相关疾病的研究提供一定的病理生理学基础。