Altered bladder function in elastin-deficient mice at baseline and in response to partial bladder outlet obstruction.
Altered bladder function in elastin-deficient mice at baseline and in response to partial bladder outlet obstruction.
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弹性蛋白缺陷小鼠的膀胱功能在基线和对部分膀胱出口梗阻的反应中发生改变。
DOI：
10.1111/j.1464-410x.2011.10773.x
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发表时间：
2012
影响因子：
4.5
通讯作者：
Chitaley,Kanchan
中科院分区：
文献类型：
--
作者：
Jiang,Xiaogang;Luttrell,Ian;Li,DeanY;Yang,ClaireC;Chitaley,Kanchan
研究类型-病因学（病例对照）证据等级3b关于该受试者已知什么？ 这项研究增加了什么？作为细胞外基质的主要成分之一，弹性纤维被认为可以增强组织的顺应性。然而，弹性纤维在正常膀胱功能和功能障碍中的作用仍然是推测性的。尽管过度表达弹性蛋白的转基因小鼠表现出膀胱顺应性增加，但在非顺应性膀胱患者中的发现并不一致。使用转基因弹性蛋白缺陷小鼠模型，这项研究提供了第一个直接证据，即足够的弹性蛋白含量对健康的膀胱功能至关重要，而弹性蛋白参与了膀胱出口部分梗阻时逼尿肌的反应。研究弹性蛋白单倍体不足小鼠（Eln+/−）在基线时以及对部分膀胱出口梗阻（pBOO）的反应时膀胱的功能和分子变化。材料和方法·研究雌性Eln +/−和野生型（Wt）小鼠（3-4月龄）。通过测量锁链素定量膀胱弹性蛋白含量。将小鼠分成两组，进行手术以产生pBOO或进行假手术。术后3天，通过活体收缩测量法评估膀胱功能，并通过活体肌电描记术检查暴露于电场刺激（EFS）和卡巴胆碱的膀胱条的收缩反应。结果·与Wt-sham小鼠相比，Eln +/−-sham小鼠膀胱弹性蛋白减少33.6%。·膀胱测压显示Eln +/−-sham与Wt-sham小鼠的膀胱顺应性和容量显著降低;与Wt小鼠相比，pBOO在更大程度上增加了Eln +/−小鼠的膀胱顺应性和容量。与Wt-sham小鼠相比，Eln +/−-sham小鼠的膀胱条对EFS和卡巴胆碱的收缩反应显著增强。在Wt-pBOO和Wt-sham小鼠中检测到对卡巴胆碱的收缩反应显着增加，而在Eln +/−-pBOO和Eln +/−-sham小鼠中没有检测到对卡巴胆碱的收缩反应显着增加。Wt-pBOO小鼠对卡巴胆碱的收缩反应增强，但Eln +/−-pBOO小鼠没有，表明弹性蛋白对于正常膀胱功能是关键，并参与膀胱对pBOO的反应。
Study Type – Aetiology (case control)Level of Evidence 3bWhat's known on the subject? and What does the study add?As one of the major components of the extracellular matrix, elastic fibres are believed to enhance tissue compliance. However, the role of elastic fibres in normal bladder function and dysfunction remains speculative. Although transgenic mice overexpressing elastin showed increased bladder compliance, the findings in patients with non‐compliant bladders are inconsistent.Using transgenic elastin‐deficient mouse models, this study provides the first direct evidence that sufficient elastin content is critical for healthy bladder function, and elastin is involved in the detrusor response to partial bladder outlet obstruction.OBJECTIVE•To examine functional and molecular changes of the bladders from elastin‐haploinsufficient mice (Eln+/−) at baseline as well as in response to partial bladder outlet obstruction (pBOO).MATERIALS AND METHODS•FemaleEln+/−and wild type (Wt) mice (3–4 months old) were studied.•The bladder elastin content was quantified by measuring desmosine.•Mice were divided into two groups to undergo surgery to create pBOO or to undergo sham surgery. Three days after surgery, bladder function was evaluated byin vivocystometry, and the contractile response of bladder strips exposed to electrical field stimulation (EFS) and carbachol was examined byex vivomyography.RESULTS•TheEln+/−‐sham mice had a 33.6% decrease in bladder elastin compared withWt‐sham mice.•Cystometry showed significantly decreased bladder compliance and capacity inEln+/−‐sham vsWt‐sham mice; pBOO increased bladder compliance and capacity to a greater extent inEln+/−mice compared withWtmice.•Bladder strips fromEln+/−‐sham mice showed a significantly heightened contractile response to both EFS and carbachol compared withWt‐sham mice.•A significantly increased contractile response to carbachol was detected inWt‐pBOO vsWt‐sham but not betweenEln+/−‐pBOO andEln+/−‐sham mice.CONCLUSION•The results that elastin‐deficient mice had decreased bladder compliance and capacity and increased bladder contractility; and thatWt‐pBOO mice showed an enhanced contractile response to carbachol, butEln+/−‐pBOO mice did not, suggest that elastin is critical for normal bladder function and is involved in bladder response to pBOO.