Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan, Republic of China.
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan, Republic of China.
J Urol. 2016 Sep;196(3):831-7. doi: 10.1016/j.juro.2016.02.2958. Epub 2016 Feb 27.
We investigated urothelial integrity, suburothelial inflammation and the expression of sensory proteins in the bladder urothelium of male patients with bladder outlet obstruction and various bladder dysfunctions.
We prospectively enrolled 33 men with urodynamically proven bladder outlet obstruction as the study group. Bladder biopsies were obtained from all study patients and 10 control patients. The expression of E-cadherin, zonula occludens-1, tryptase, apoptosis, TRPV (transient receptor potential vanilloid) 1 and 4, β3 adrenoreceptor, M2 and M3 muscarinic receptors, P2X3 receptor, and inducible/epithelial nitric oxide synthase were compared between study and control patients.
Study patients had significantly lower expression of E-cadherin, and a higher number of suburothelial mast and apoptotic cells than controls. Additionally, higher expression of P2X3 and M2 muscarinic receptors, and lower expression of M3 muscarinic receptor were detected in study patients. The detrusor underactivity subgroup was characterized by significantly higher expression of β3 adrenoreceptors and lower expression of inducible nitric oxide synthase than in controls. In study patients a significantly positive correlation was noted between voided volume and E-cadherin expression (r = 0.372), volume at first sensation of filling and β3 adrenoreceptor expression (r = 0.386), and detrusor pressure and M2 muscarinic receptor expression (r = 0.496) in the bladder urothelium (each p <0.05).
Urothelial dysfunction, suburothelial inflammation, cellular apoptosis and alterations in sensory proteins are prominent in bladder dysfunction secondary to bladder outlet obstruction. Impaired urothelial signaling and sensory transduction pathways appear to reflect the pathophysiology of bladder dysfunction and detrusor underactivity in patients with bladder outlet obstruction.
我们研究了男性膀胱出口梗阻和各种膀胱功能障碍患者的膀胱尿路上皮完整性、下尿路炎症和感觉蛋白表达。
前瞻性纳入 33 例经尿动力学证实的膀胱出口梗阻患者作为研究组。所有研究患者和 10 例对照组患者均获得膀胱活检。比较研究组和对照组患者 E-钙黏蛋白、紧密连接蛋白-1、胰蛋白酶、细胞凋亡、瞬时受体电位香草酸 1 和 4、β3 肾上腺素能受体、M2 和 M3 毒蕈碱受体、P2X3 受体和诱导型/上皮型一氧化氮合酶的表达。
与对照组相比，研究组患者 E-钙黏蛋白表达显著降低，下尿路平滑肌和凋亡细胞数量明显增加。此外，研究组患者 P2X3 和 M2 毒蕈碱受体表达较高，M3 毒蕈碱受体表达较低。逼尿肌功能低下亚组与对照组相比，β3 肾上腺素能受体表达明显升高，诱导型一氧化氮合酶表达明显降低。在研究组患者中，尿排空量与 E-钙黏蛋白表达呈显著正相关（r = 0.372），首次感觉充盈量与β3 肾上腺素能受体表达呈显著正相关（r = 0.386），逼尿肌压与 M2 毒蕈碱受体表达呈显著正相关（r = 0.496）（均 p<0.05）。
膀胱出口梗阻引起的膀胱功能障碍患者存在明显的尿路上皮功能障碍、下尿路炎症、细胞凋亡和感觉蛋白改变。受损的尿路上皮信号和感觉转导通路似乎反映了膀胱出口梗阻患者膀胱功能障碍和逼尿肌功能低下的病理生理学。
