The Antimuscarinic Agent Tolterodine Regulates Bladder Extracellular Matrix in Partial Bladder Outlet Obstruction in Rats
The Antimuscarinic Agent Tolterodine Regulates Bladder Extracellular Matrix in Partial Bladder Outlet Obstruction in Rats
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DOI：
10.1159/000488407
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发表时间：
2018-03
影响因子：
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通讯作者：
Tongxin Yang;D. Luo;Yifei Lin;Qiang Liu;Xiang Cai;J. Ai;Hong Li;Hong Shen;Kun-jie Wang
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文献类型：
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作者：
Tongxin Yang;D. Luo;Yifei Lin;Qiang Liu;Xiang Cai;J. Ai;Hong Li;Hong Shen;Kun-jie Wang
背景/目的：抗毒蕈碱药物可以延缓膀胱出口梗阻（BOO）引起的膀胱功能障碍的进展。迄今为止，毒蕈碱受体活性和膀胱细胞外基质（ECM）之间的关系仍不清楚。因此，在雌性大鼠中建立部分BOO（PBOO）的动物模型，以探索在PBOO条件下施用抗毒蕈碱剂时膀胱壁ECM蛋白的变化。方法：将大鼠随机分为假手术组、PBOO组和PBOO+托特罗定组。天狼星红染色法检测膀胱平滑肌和胶原含量。采用基因芯片技术和RT-PCR技术检测大鼠膀胱组织中ECM蛋白、受体和代谢调节因子的表达。通过免疫组化进一步评价阳性结果。结果如下：苦味酸天狼猩红染色显示PBOO组和PBOO+托特罗定组平滑肌体积显著增加（p < 0.05），而PBOO组胶原显著增加（p < 0.05），而PBOO+托特罗定组无此变化。基因芯片和RT-PCR显示，没有胶原亚型表现出显着的变化后，PBOO建立和托特罗定管理。而PBOO加托特罗定组的基质金属蛋白酶（MMPs）显著升高（p < 0.05）。此外，PBOO抑制大鼠膀胱壁中非胶原ECM蛋白的表达，而托特罗定诱导非胶原ECM蛋白和ECM受体的表达。结论：托特罗定可能通过MMPs减少PBOO大鼠膀胱壁胶原的体积，并调节ECM蛋白及其受体的表达。
Background/Aims: Antimuscarinic agents can delay the progression of bladder dysfunction caused by bladder outlet obstruction (BOO). To date, the relationship between muscarinic receptor activity and the bladder extracellular matrix (ECM) remains unclear. Thus, an animal model of partial BOO (PBOO) in female rats was established to explore the variation in bladder wall ECM proteins under PBOO conditions with antimuscarinic agent administration. Methods: Rats were randomly divided into three groups: sham, PBOO, and PBOO plus tolterodine. Picrosirius red staining was used to examine the smooth muscle and collagen content of bladder samples. Gene microarray and RT-PCR were performed to survey the expression of ECM proteins, receptors, and metabolism regulators in the rat bladder. Positive results were further evaluated by immunohistochemistry. Results: Picrosirius red staining showed that smooth muscle volume significantly increased in the PBOO and PBOO plus tolterodine groups (p < 0.05), while collagen significantly increased in the PBOO group (p < 0.05) but not in the PBOO plus tolterodine group. Gene microarray and RT-PCR revealed that none of the collagen subtypes exhibited significant changes after PBOO establishment and tolterodine administration. However, matrix metalloproteinases (MMPs) increased significantly in the PBOO plus tolterodine group (p < 0.05). Additionally, PBOO inhibited the expression of non-collagen ECM proteins in the rat bladder wall, while tolterodine induced the expression of non-collagen ECM proteins and ECM receptors. Conclusions: Tolterodine decreased the volume of collagen in PBOO rat bladder wall, possibly via MMPs, and regulated the expression of ECM proteins and receptors.