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特定 microRNAs 在脊髓损伤小鼠模型中的时空表达水平及其与压迫持续时间的关系。

Spatial and temporal expression levels of specific microRNAs in a spinal cord injury mouse model and their relationship to the duration of compression.

机构信息

Department of Neurosurgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive (MC 7843), San Antonio, TX 78229, USA.

Department of Neurosurgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive (MC 7843), San Antonio, TX 78229, USA.

出版信息

Spine J. 2014 Feb 1;14(2):353-60. doi: 10.1016/j.spinee.2013.08.015. Epub 2013 Oct 23.

DOI:10.1016/j.spinee.2013.08.015
PMID:24269082
Abstract

BACKGROUND CONTEXT

MicroRNAs, a class of small nonprotein-coding RNAs, are thought to control gene translation into proteins. The latter are the ultimate effectors of the biochemical cascade occurring in any physiological and pathological process. MicroRNAs have been shown to change their expression levels during injury of spinal cord in contusion rodent models. Compression is the most frequent mode of damage of neural elements in spinal cord injury. The cellular and molecular changes occurring in the spinal cord during prolonged compression are not very well elucidated. Understanding the underlying molecular events that occur during sustained compression is paramount in building new therapeutic strategies.

PURPOSE

The purpose of our study was to probe the relationship between the expression level changes of different miRNAs and the timing of spinal cord decompression in a mouse model.

STUDY DESIGN

A compression spinal cord injury mouse model was used for the study.

METHODS

A laminectomy was performed in the thoracic spine of C57BL/6 mice. Then, the thecal sac was compressed to create the injury. Decompression was performed early for one group and it was delayed in the second group. The spinal cord at the epicenter of the injury and one level rostral to it were removed at 3, 6, and 24 hours after trauma, and RNA was extracted. Expression levels of six different microRNAs and the relationship to the duration of compression were analyzed. This work was supported in part by the University Research Council Grants Program at the University of Texas Health Science Center San Antonio (Grant 130267). There are no specific conflicts of interest to be disclosed for this work.

RESULTS

Expression levels of microRNAs in the prolonged compression of spinal cord model were significantly different compared with the expression levels in the short duration of compression spinal cord injury model. Furthermore, microRNAs show a different expression pattern in different regions of the injured spinal cord.

CONCLUSIONS

Our findings demonstrate that spinal cord compression causes alterations in the expression of different miRNAs in the acute phase of injury. Their expression is related to the duration of the compression of the spinal cord. These findings suggest that early decompression of the spinal cord may have an important modulating effect on the molecular cascade triggered during secondary injury through the changes in expression levels of specific microRNAs.

摘要

背景

微小 RNA(miRNA)是一类小型非蛋白编码 RNA,被认为可以控制基因翻译为蛋白质。后者是任何生理和病理过程中生化级联反应的最终效应物。研究表明,在挫伤性啮齿动物脊髓损伤模型中,miRNA 的表达水平会发生变化。压迫是脊髓损伤中神经元素最常见的损伤方式。脊髓在长时间压迫下发生的细胞和分子变化尚不清楚。了解持续压迫过程中发生的潜在分子事件对于构建新的治疗策略至关重要。

目的

本研究旨在探讨不同 miRNA 的表达水平变化与小鼠模型中脊髓减压时间的关系。

研究设计

本研究采用压迫性脊髓损伤小鼠模型。

方法

在 C57BL/6 小鼠的胸段脊柱进行椎板切除术,然后对硬脊膜囊进行压迫以造成损伤。一组进行早期减压,另一组进行延迟减压。创伤后 3、6 和 24 小时,从损伤中心和一个近端节段取出脊髓,提取 RNA。分析 6 种不同 microRNA 的表达水平及其与压迫持续时间的关系。本工作部分得到德克萨斯大学健康科学中心圣安东尼奥分校大学研究理事会资助计划(Grant 130267)的支持。本工作无具体利益冲突。

结果

与短暂压迫性脊髓损伤模型相比,长时间压迫性脊髓模型中 microRNA 的表达水平明显不同。此外,miRNA 在损伤脊髓的不同区域表现出不同的表达模式。

结论

我们的研究结果表明,脊髓压迫导致损伤急性期不同 miRNA 的表达发生改变。其表达与脊髓压迫持续时间有关。这些发现表明,脊髓的早期减压可能通过特定 microRNA 表达水平的变化对继发性损伤触发的分子级联反应产生重要的调节作用。

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