PDF(Pubmed)
Abstract：
This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-β1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFβ-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.
摘要：
这项研究调查了hAFSCs是否可以通过靶向特定的细胞途径来改善部分膀胱出口梗阻（pBOO）大鼠的膀胱功能。将36只雌性大鼠分为假手术组和pBOO组，分别向膀胱壁注射和不注射hAFSC。测压,炎症/缺氧，胶原/纤维化/间隙连接蛋白，在pBOO或假手术后2和6周检查平滑肌肌球蛋白/毒蕈碱受体。在pBOO膀胱中，峰值排尿压力和残余体积的显着增加刺激了炎症和缺氧因素的显着上调，TGF-β1和Smad2/3。胶原沉积蛋白,胶原蛋白1和3，显着增加，但是膀胱纤维化标志物，小窝蛋白1和3均显着降低。间隙连接细胞间通讯蛋白,连接蛋白43，显着增加，但是小窝的数量明显减少。平滑肌表型的标志物，肌球蛋白重链11和鸟苷酸依赖性蛋白激酶，以及M2毒蕈碱受体，在培养的逼尿肌细胞中显著增加。然而,hAFSCs治疗可通过抑制TGFβ-Smad信号通路显著改善膀胱功能障碍,减少胶原蛋白沉积，破坏间隙连接细胞间通讯，并改变平滑肌肌球蛋白和小窝/小窝蛋白的表达。结果支持基于hAFSCs治疗BOO患者膀胱功能障碍的潜在价值。
