Liang Ching-Chung, Shaw Steven W, Huang Yung-Hsin, Lee Tsong-Hai
Female Urology Section, Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Division of Obstetrics, Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 105, Taiwan.
World J Stem Cells. 2022 May 26;14(5):330-346. doi: 10.4252/wjsc.v14.i5.330.
Diabetes mellitus (DM) is a serious and growing global health burden. It is estimated that 80% of diabetic patients have micturition problems such as poor emptying, urinary incontinence, urgency, and urgency incontinence. Patients with diabetic bladder dysfunction are often resistant to currently available therapies. It is necessary to develop new and effective treatment methods.
To examine the therapeutic effect of human amniotic fluid stem cells (hAFSCs) therapy on bladder dysfunction in a type 2 diabetic rat model.
Sixty female Sprague-Dawley rats were divided into five groups: Group 1, normal-diet control (control); group 2, high-fat diet (HFD); group 3, HFD plus streptozotocin-induced DM (DM); group 4, DM plus insulin treatment (DM + insulin); group 5, DM plus hAFSCs injection tail vein (DM + hAFSCs). Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure, voided volume, intercontraction interval, bladder capacity, and residual volume. Immunoreactivities and/or mRNA expression of muscarinic receptors, nerve growth factor (NGF), and sensory nerve markers in the bladder and insulin, MafA, and pancreatic-duodenal homeobox-1 (PDX-1) in pancreatic beta cells were studied.
Compared with DM rats, insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume, intercontraction interval, bladder capacity, and residual volume ( < 0.05). However, both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls ( > 0.05). The immunoreactivities and mRNA expression of M2- and M3-muscarinic receptors (M2 and M3) were increased mainly at 4 wk ( < 0.05), while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF, calcitonin gene-related peptide (CGRP), substance P, insulin, MafA, and PDX-1 were decreased in DM rats ( < 0.05). However, insulin and hAFSCs treatment could help to regain the expression of M2, M3, NGF, CGRP, substance P, MafA, and PDX-1 to near the levels of controls at 4 and/or 12 wk ( > 0.05).
Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM; however, hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.
糖尿病(DM)是一个严重且日益加重的全球健康负担。据估计,80%的糖尿病患者存在排尿问题,如排空障碍、尿失禁、尿急和急迫性尿失禁。糖尿病膀胱功能障碍患者通常对现有治疗方法耐药。因此,有必要开发新的有效治疗方法。
研究人羊水干细胞(hAFSCs)治疗对2型糖尿病大鼠模型膀胱功能障碍的疗效。
将60只雌性Sprague-Dawley大鼠分为五组:第1组,正常饮食对照组(对照组);第2组,高脂饮食组(HFD);第3组,高脂饮食加链脲佐菌素诱导的糖尿病组(DM);第4组,DM加胰岛素治疗组(DM +胰岛素);第5组,DM加hAFSCs尾静脉注射组(DM + hAFSCs)。在胰岛素或hAFSCs治疗后4周和12周进行清醒膀胱测压研究,以测量排尿峰值压力、排尿量、收缩间期、膀胱容量和残余尿量。研究膀胱中M胆碱受体、神经生长因子(NGF)和感觉神经标志物的免疫反应性和/或mRNA表达,以及胰岛β细胞中胰岛素、MafA和胰腺十二指肠同源盒-1(PDX-1)的表达。
与DM大鼠相比,胰岛素治疗而非hAFSCs治疗可减轻膀胱重量,并改善排尿量、收缩间期、膀胱容量和残余尿量(P<0.05)。然而,胰岛素和hAFSCs治疗均有助于使血糖和膀胱功能恢复至接近对照组的水平(P>0.05)。M2和M3型M胆碱受体(M2和M3)的免疫反应性和mRNA表达主要在4周时增加(P<0.05),而DM大鼠胰岛中β细胞数量以及NGF、降钙素基因相关肽(CGRP)、P物质、胰岛素、MafA和PDX-1的免疫反应性和/或mRNA表达均降低(P<0.05)。然而,胰岛素和hAFSCs治疗可使M2、M3、NGF、CGRP、P物质、MafA和PDX-1在4周和/或12周时的表达恢复至接近对照组的水平(P>0.05)。
胰岛素治疗而非hAFSCs治疗可恢复DM所致的膀胱功能障碍;然而,hAFSCs和胰岛素治疗可使膀胱功能恢复至接近对照组的水平。