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基于基因组的大鼠脊髓损伤后表达谱研究:48 基因模型阵列。

Genome-based expression profiling study following spinal cord injury in the rat: An array of 48-gene model.

机构信息

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and University of Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan, Taiwan.

出版信息

Neurourol Urodyn. 2010 Nov;29(8):1439-43. doi: 10.1002/nau.20769.

Abstract

AIM

To explore the potential molecular mechanisms underlying experimental neurogenic bladder dysfunction.

METHODS

With the aid of Affymetrix GeneChip Rat Genome U34A arrays, we examined microarray gene expression profiles in bladder wall tissue from female Sprague-Dawley rats within the first 3 weeks following spinal cord injury. Gene transcripts expressed in rat bladder wall tissue at 3 days, 7 days, and 3 weeks following spinal cord injury were compared to normal rat bladder wall tissue.

RESULTS

The Mahalanobis distance in hierarchical cluster analysis revealed a 48-gene model, which contained high expressions in rat bladder wall tissue at 3 days, 7 days, and 3 weeks following spinal cord injury. According to gene ontology, plausible molecular alterations in rat bladder wall tissue following spinal cord injury include: (1) the release of nerve growth factor (NGF) and transforming growth factor beta 1 (Tgfb1) (2) the secretion of histamine from mast cells, (3) the occurrence of blood coagulation, (4) the occurrence of N-terminal protein myristoylation, and (5) Axon guidance mediated by Ena/Vasodilator-stimulated phosphoprotein (Ena/VASP) promotes reestablishment of the bladder reflex following spinal cord injury. Such changes, jointly termed "bladder remodeling," can constitute an important long-term consequence of neurogenic bladder dysfunction.

CONCLUSION

The success of this innovation has supported the use of microarray-based expression profiling as a commonplace platform for the pathogenesis and therapeutic interventions of experimental neurogenic bladder dysfunction. dysfunction.

摘要

目的

探索实验性神经源性膀胱功能障碍的潜在分子机制。

方法

借助 Affymetrix GeneChip Rat Genome U34A 阵列,我们检测了脊髓损伤后第 1 至 3 周内雌性 Sprague-Dawley 大鼠膀胱壁组织中的微阵列基因表达谱。将脊髓损伤后 3 天、7 天和 3 周大鼠膀胱壁组织中表达的基因转录物与正常大鼠膀胱壁组织进行比较。

结果

层次聚类分析中的马氏距离揭示了一个包含 48 个基因的模型,该模型在脊髓损伤后 3 天、7 天和 3 周的大鼠膀胱壁组织中高表达。根据基因本体论,脊髓损伤后大鼠膀胱壁组织中可能发生的分子改变包括:(1)神经生长因子(NGF)和转化生长因子β 1(Tgfb1)的释放;(2)肥大细胞中组胺的分泌;(3)血液凝固的发生;(4)N 端蛋白豆蔻酰化的发生;(5)Ena/Vasodilator-stimulated phosphoprotein(Ena/VASP)介导的轴突导向促进了脊髓损伤后膀胱反射的重新建立。这些变化共同称为“膀胱重塑”,是神经源性膀胱功能障碍的重要长期后果之一。

结论

这项创新的成功支持了将基于微阵列的表达谱分析作为实验性神经源性膀胱功能障碍的发病机制和治疗干预的常用平台。

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