Diabetic bladder dysfunction progresses from an overactive to an underactive phenotype in a type-1 diabetic mouse model (Akita female mouse) and is dependent on NLRP3.
Diabetic bladder dysfunction progresses from an overactive to an underactive phenotype in a type-1 diabetic mouse model (Akita female mouse) and is dependent on NLRP3.
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DOI：
10.1016/j.lfs.2022.120528
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发表时间：
2022-06-15
期刊：
影响因子：
6.1
通讯作者：
Purves, J. Todd
中科院分区：
文献类型：
--
作者：
Hughes, Francis M., Jr.;Allkanjari, Armand;Odom, Michael R.;Jin, Huixia;Purves, J. Todd
糖尿病膀胱功能障碍（DBD）是一种常见的糖尿病并发症，被认为是从膀胱过度活动（OAB）发展到膀胱活动不足（UAB）。以前我们在秋田小鼠（一种1型糖尿病的遗传模型）中发现了15周时的OAB。本研究的第一个目的是在30周时评估膀胱功能以评估进展。此外，由NLRP 3炎性体触发的炎症与DBD有关。在第二个目标中，我们通过将秋田小鼠与NLRP 3 −/−小鼠杂交来评估NLRP 3的作用。秋田小鼠与NLRP 3 −/−小鼠交配。通过比较非糖尿病小鼠与糖尿病小鼠（所有NLRP 3 +/+）来评估糖尿病的影响。通过比较非糖尿病/NLRP 3 −/−与糖尿病/NLRP 3 −/−小鼠，评估了在NLRP 3炎性体缺失的情况下糖尿病的影响。在30周时评估小鼠的血糖（血糖仪）、炎症（伊文思蓝）、膀胱形态（组织学）和膀胱功能（尿动力学）。在30周时，非糖尿病患者和糖尿病患者的血糖不受NLRP 3存在或缺失的影响。糖尿病/NLRP 3 +/+小鼠表现出膀胱炎症和逼尿肌肥大，这在糖尿病/NLRP 3 −/−小鼠中被阻断，清楚地显示了NLRP 3的作用。当检查膀胱功能时，糖尿病/NLRP 3 +/+显示排尿量增加和频率降低，这是膀胱活动不足的两个体征。然而，在NLRP 3 −/−小鼠中，糖尿病无法实现这些变化，这表明NLRP 3诱导的炎症是这些小鼠中UAB症状的原因。秋田糖尿病小鼠从OAB进展为UAB。NLRP 3是治疗DBD的一个可能的靶点。
Diabetic bladder dysfunction (DBD) is a prevalent diabetic complication thought to progress from overactive (OAB) to underactive (UAB) bladder. Previously we found OAB at 15 weeks in the Akita mouse, a genetic model of Type 1 diabetes. The first aim of this study assesses bladder function at 30 weeks to assess progression. In addition, inflammation triggered by the NLRP3 inflammasome is implicated in DBD. In a second aim we assessed a role for NLRP3 by crossing Akita mice with NLRP3−/− mice. Akita mice were bred with NLRP3−/− mice. The effect of diabetes was assessed by comparing nondiabetic to diabetic mice (all NLRP3+/+). The effect of diabetes in the absence of the NLRP3 inflammasome was assessed by comparing nondiabetic/NLRP3−/− to diabetic/NLRP3−/− mice. Mice were assessed at 30 weeks for blood glucose (glucometer), inflammation (Evans blue), bladder morphology (histology) and bladder function (urodynamics). At 30 weeks blood glucose of nondiabetics and diabetics was not affected by the presence of absence of NLRP3. Diabetic/NLRP3+/+ mice showed bladder inflammation and detrusor hypertrophy which was blocked in the diabetic/NLRP3−/− mice, clearly showing a role for NLRP3. When bladder function was examined, diabetic/NLRP3+/+ showed an increase in voiding volume and a decrease in frequency, two signs of underactive bladder. However, in the NLRP3−/− mice, diabetes was unable to effectuate these changes, demonstrating that NLRP3-induced inflammation is responsible for UAB symptoms in these mice Akita diabetic mice progress from OAB to UAB. NLRP3 is a possible target to treat DBD.
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影响因子：
9.1
作者：
Fulop T;Larbi A;Pawelec G;Khalil A;Cohen AA;Hirokawa K;Witkowski JM;Franceschi C
通讯作者：
Franceschi C
影响因子：
6.6
作者：
Daneshgari, Firouz;Liu, Guiming;Imrey, Peter B.
通讯作者：
Imrey, Peter B.
DOI：
10.1152/ajprenal.00297.2013
发表时间：
2014-02-01
影响因子：
4.2
作者：
Hughes, Francis M., Jr.;Vivar, Nivardo P.;Purves, J. Todd
通讯作者：
Purves, J. Todd
影响因子：
6.6
作者：
EIKA, B;LEVIN, RM;LONGHURST, PA
通讯作者：
LONGHURST, PA
DOI：
10.1016/j.juro.2009.08.070
发表时间：
2009-12
期刊：
The Journal of urology
影响因子：
--
作者：
Daneshgari F;Liu G;Birder L;Hanna-Mitchell AT;Chacko S
通讯作者：
Chacko S