The NLRP3 Inflammasome Mediates Inflammation Produced by Bladder Outlet Obstruction.
The NLRP3 Inflammasome Mediates Inflammation Produced by Bladder Outlet Obstruction.
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DOI：
10.1016/j.juro.2015.12.068
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Purves JT
中科院分区：
文献类型：
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作者：
Hughes FM Jr;Hill HM;Wood CM;Edmondson AT;Dumas A;Foo WC;Oelsen JM;Rac G;Purves JT
虽然膀胱出口梗阻（BOO）是公认的引起膀胱炎症反应，导致膀胱过度活动症和纤维化，很少有人知道的机制，这是启动。Nod-Like Receptors（NLR）和它们形成的结构（炎性小体）已被鉴定为细胞损伤（包括压力诱导的损伤）的传感器和炎症的触发器。最近，我们发现这些结构在尿道。在这项研究中，我们评估了NLRP 3炎性小体在BOO引起的膀胱功能障碍中的作用。在雌性大鼠中通过插入Imm（o.d.）经尿道导管，在尿道周围系上丝线并取出导管。未处理和假手术大鼠作为对照。给予BOO大鼠媒介物（10%乙醇）或10 mg/kg格列本脲（一种NLRP 3抑制剂;每天一次，持续12天，p.o.）。评估炎性小体活性、膀胱肥大、炎症和膀胱功能（尿动力学）。结果：BOO增加尿路上皮炎性小体活性、膀胱肥大和炎症，并减少排尿量。格列本脲阻断炎性小体活化，减少肥大并预防炎症。格列本脲也可通过延长逼尿肌收缩时间和排尿期来减弱排尿量的减少。结果表明NLRP 3炎性体在诱导继发于BOO的炎症和膀胱功能障碍中的重要性。用NLRP 3抑制剂阻止这些过程可能有助于治疗它们产生的症状。
While bladder outlet obstruction (BOO) is well-established to elicit an inflammatory reaction in the bladder that leads to overactive bladder and fibrosis, little is known about the mechanism by which this is initiated. Nod-Like Receptors (NLRs) and the structures they form (inflammasomes) have been identified as sensors of cellular damage (including pressure-induced damage) and triggers of inflammation. Recently, we identified these structures in the urothelium. In this study we assess the role of the NLRP3 inflammasome in the bladder dysfunction resulting from BOO. BOO was created in female rats by insertion of a 1 mm (o.d.) transurethral catheter, tying a silk ligature around the urethra and removing the catheter. Untreated and sham-operated rats served as controls. BOO rats were given vehicle (10% ethanol) or 10 mg/kg of glyburide (an NLRP3 inhibitor; daily for 12 days, p.o.). Inflammasome activity, bladder hypertrophy, inflammation and bladder function (urodynamics) were assessed. Results: BOO increased urothelial inflammasome activity, bladder hypertrophy, and inflammation and reduced voiding volume. Glyburide blocked inflammasome activation, reduced hypertrophy and prevented inflammation. The reduction in void volume was also attenuated by glyburide, mechanistically by an increase in the duration of detrusor contraction and voiding period. The results suggest the importance of the NLRP3 inflammasome in the induction of inflammation and bladder dysfunction secondary to BOO. Arresting these processes with NLRP3 inhibitors may prove useful in treating the symptoms they produce.