Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction
Protective Effects of Antimuscarinics on the Bladder Remodeling After Bladder Outlet Obstruction
复制标题
抗毒蕈碱药对膀胱出口梗阻后膀胱重塑的保护作用
DOI：
10.1159/000485358
复制
发表时间：
2017-01-01
影响因子：
--
通讯作者：
Wang, Kunjie
中科院分区：
文献类型：
--
作者：
Liu, Qiang;Luo, Deyi;Wang, Kunjie
背景/目的：与膀胱出口梗阻（BOO）相关的膀胱过度活动症是一种非常普遍的疾病，通常用抗毒蕈碱药物治疗。然而，迄今为止，尚未研究抗毒蕈碱药对膀胱结构和功能的潜在影响。方法：Sprague-Dawley(R) 大鼠接受膀胱颈梗阻手术或假手术，然后接受三种不同的抗毒蕈碱药（索利那新、达非那新和托特罗定）或载体治疗。 3、6和12周后，测量膀胱功能和结构。在机械刺激下观察抗毒蕈碱药对体外细胞改变的影响。采用免疫组织化学法检测膀胱形态，采用膀胱测压和条带收缩试验检测膀胱功能。通过PCR和蛋白质印迹法测量毒蕈碱受体和炎症细胞因子的表达。结果：在这里，我们在体外和体内证明抗毒蕈碱药是膀胱结构和功能的保护性调节剂。抗毒蕈碱药可减轻 BOO 膀胱的重量。抗毒蕈碱药改善排尿参数并增强膀胱平滑肌的收缩。研究结果还表明，抗毒蕈碱药在体内和体外均能抑制膀胱平滑肌细胞的增殖，可以减少BOO膀胱内的胶原沉积和炎症细胞因子。在此过程中，M2 和 M3 受体的表达被抗毒蕈碱药改变。结论：抗毒蕈碱药物能够在细胞和组织水平上逆转BOO膀胱壁的结构和功能变化，M2和M3受体的改变可能参与了这一生物学过程。
Background/Aims: Overactive bladder associated with bladder outlet obstruction (BOO) is a highly prevalent condition, which is usually treated with antimuscarinics. However, the potential effects of antimuscarinics on the structure and function of bladder have not been investigated thus far. Methods: Sprague-Dawley(R) rats accepted bladder neck obstruction surgery or sham surgery, and then received treatment of three different antimuscarinics (Solifenacin, Darifenacin, and Tolterodine) or vehicle. After 3, 6 and 12 weeks, the bladder function and structure were measured. The effect of antimuscarinics on cellular alteration in vitro was observed under mechanical stimulation. Bladder morphology were examined by immunohistochemistry, and the bladder function were investigated by cystometry and strip contractility test. The expression of muscarinic receptors and inflammatory cytokines were measured by PCR and Western blotting. Results: Here we demonstrate, both in vitro and in vivo, that antimuscarinics are protective regulators for the bladder structure and function. Antimuscarinics decrease the weight of bladders with BOO. Antimuscarinics improve the voiding parameter and enhance the contraction of bladder smooth muscle. The results also show that antimuscarinics inhibit the proliferation of bladder smooth muscle cells both in vivo and in vitro, it can reduce the collagen deposition and inflammatory cytokines in bladders with BOO. During this process, the expression of M2 and M3 receptors was altered by antimuscarinics. Conclusion: Antimuscarinics could reverse the structural and functional changes of BOO bladder wall at cellular and tissue level, and the alteration of M2 and M3 receptors may be involved in this biological process.