Diabetic bladder dysfunction in T2D KK-Ay mice and its changes in the level of relevant gene expression.
Diabetic bladder dysfunction in T2D KK-Ay mice and its changes in the level of relevant gene expression.
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DOI：
10.1016/j.biopha.2020.110706
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
jiao Zhang;Yao Zhang;Xu-feng Yang;Jing Wang;Yi-fei Xu;Rui Wang;Bo Tan;Ping Huang;H. Cao
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文献类型：
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作者：
jiao Zhang;Yao Zhang;Xu-feng Yang;Jing Wang;Yi-fei Xu;Rui Wang;Bo Tan;Ping Huang;H. Cao
糖尿病膀胱功能障碍（diabetic bladder dysfunction，DBD）是糖尿病（diabetes mellitus，DM）最常见、最棘手的并发症之一。方法将27只KK-Ay小鼠和30只C57 BL/6 J小鼠随机分为12、18和25周龄组，每组10只。在不同时间点测量体重、饮水量、排尿量、排尿次数、空腹血糖（FBG）、口服葡萄糖耐量试验（OGTT）。采用尿动力学试验测定最大膀胱容量（MBC）、残余容量（RV）、膀胱顺应性（BC）、排尿效率（VE）和最大排尿压（MVP），逼尿肌条收缩试验测定对α，β-亚甲基ATP、KCl、电场刺激、卡巴胆碱的收缩反应。膀胱用苏木精和伊红（H&E）和Masson三色染色以确定膀胱壁厚度。结果KK-Ay小鼠体重、饮水量、排尿量、排尿频率、空腹血糖、血糖AUC 0 - 2 h在3个时间点均显著增加，与对照组比较差异有统计学意义（P < 0. 05）。MBC、RV和BC显著增加; KK-Ay小鼠在18和25周龄时VE显著降低; KK-Ay小鼠在25周龄时MVP显著增加。在DSM条收缩试验中，KK-Ay小鼠的自发活动幅度在12周龄和18周龄时显著增加，而在25周龄时幅度和频率均显著降低。KK-Ay小鼠12周时肌球蛋白Va、SLC 17 A9和M3受体水平显著降低，18周时肌球蛋白Va水平显著升高; KK-Ay小鼠的P2 X1和M2受体在所有三个时间点均显著增加。这项研究表明，KK-Ay小鼠是研究DBD的理想模型，其从代偿状态向失代偿状态的转变可能与肌球蛋白Va、SLC 17 A9、P2 X1、M3和M2表达水平。
ObjectiveDiabetic bladder dysfunction (DBD) is one of the most common and bothersome complications of diabetes mellitus (DM). The purpose of the present study is to investigate DBD in KK-Ay mice, and to identify the expression of relative genes.MethodTotally twenty-seven KK-Ay mice and thirty C57BL/6 J mice, respectively, were randomly divided into 12-, 18-, and 25-week old groups. The weight, water intake, voided volume, the frequency of micturition, fasting blood glucose (FBG), oral glucose tolerance test (OGTT) were measured at varying time points. Maximum bladder volume (MBC), residual volume (RV), bladder compliance (BC), micturition efficiency (VE) and maximum micturition pressure (MVP) were assessed by urodynamic test, and contractile responses to α, β‐methylene ATP, KCl, electrical‐field stimulation, carbachol were performed by detrusor smooth muscle strips contractility test. The bladders were stained with hematoxylin and eosin (H&E) and Masson’s trichrome to determine bladder wall thickness. Additionally, the mRNA expression of Myosin Va, SLC17A9, P2X1, M3 and M2 were then verified by qRT-PCR.ResultThe weight, water intake, voided volumes, micturition frequency, FBG, the blood glucose AUC0-2hof KK-Ay mice were significantly increased at three time points. MBC, RV and BC were significantly increased; VE was significantly lower at the age of 18 and 25 weeks in KK-Ay mice; MVP was significantly increased at the age of 25 weeks in KK-Ay mice. In DSM strips contractility test, the amplitude of the spontaneous activity in KK-Ay mice significant increased at 12 weeks and 18 weeks, while both the amplitude and frequency were significantly decreased at the age of 25 weeks. The level of Myosin Va, SLC17A9 and M3 receptor significantly decreased in KK-Ay mice at 12 weeks, while Myosin Va markedly increased at 18 weeks; P2X1 and M2 receptors of KK-Ay mice was significantly increased at all three time points.ConclusionTaken together, this study demonstrates that KK-Ay mice can be a proper model to investigate DBD whose transformation from compensatory state to decompensated state may ascribe to the time-dependent alternations of Myosin Va, SLC17A9, P2X1, M3 and M2 expression levels.