Functional constipation induces bladder overactivity associated with upregulations of Htr2 and Trpv2 pathways.
Functional constipation induces bladder overactivity associated with upregulations of Htr2 and Trpv2 pathways.
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功能性便秘诱导与Htr2和Trpv2通路上调相关的膀胱过度活动。
DOI：
10.1038/s41598-020-80794-0
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发表时间：
2021-01-13
影响因子：
4.6
通讯作者：
Wilcox DT
中科院分区：
文献类型：
--
作者：
Iguchi N;Carrasco A Jr;Xie AX;Pineda RH;Malykhina AP;Wilcox DT
膀胱和肠功能障碍（BBD）是一种常见但诊断不足的儿科疾病，描述了下尿路症状（LUTS），伴有表现为便秘和/或大便失禁的异常肠道模式。LUTS通常表现为尿急、尿频、尿失禁和尿路感染（UTI）。尽管越来越多的人认识到BBD是长期泌尿道问题的危险因素，包括复发性UTI，膀胱输尿管反流和肾瘢痕，但BBD的潜在机制尚不清楚，治疗仍然是经验性的。我们研究了便秘如何影响下尿路功能使用功能性便秘的幼年小鼠模型。功能性便秘4天后，动物出现LUTS，包括通过清醒膀胱测压评估的尿频和逼尿肌过度活动。使用离体膀胱条对体外逼尿肌功能进行的生理学检查表明，在不影响电场刺激、卡巴胆碱和KCl的收缩力的情况下，自发收缩显著增加。在便秘小鼠的膀胱中观察到5-羟色胺受体Htr 2a和Htr 2c显著上调，在膀胱条与0.5 µM 5-羟色胺预孵育后自发收缩增强。这些结果表明，便秘引起逼尿肌过度活动和兴奋性5-羟色胺受体激活膀胱，这有助于BBD的发展。
Bladder and bowel dysfunction (BBD) is a common yet underdiagnosed paediatric entity that describes lower urinary tract symptoms (LUTS) accompanied by abnormal bowel patterns manifested as constipation and/or encopresis. LUTS usually manifest as urgency, urinary frequency, incontinence, and urinary tract infections (UTI). Despite increasing recognition of BBD as a risk factor for long-term urinary tract problems including recurrent UTI, vesicoureteral reflux, and renal scarring, the mechanisms underlying BBD have been unclear, and treatment remains empirical. We investigated how constipation affects the lower urinary tract function using a juvenile murine model of functional constipation. Following four days of functional constipation, animals developed LUTS including urinary frequency and detrusor overactivity evaluated by awake cystometry. Physiological examination of detrusor function in vitro using isolated bladder strips, demonstrated a significant increase in spontaneous contractions without affecting contractile force in response to electrical field stimulation, carbachol, and KCl. A significant upregulation of serotonin receptors, Htr2a and Htr2c, was observed in the bladders from mice with constipation, paralleled with augmented spontaneous contractions after pre-incubation of the bladder strips with 0.5 µM of serotonin. These results suggest that constipation induced detrusor overactivity and increased excitatory serotonin receptor activation in the urinary bladder, which contributes to the development of BBD.
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DOI：
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