Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Pawinskiego 3c, 02-106 Warsaw, Poland.
Department of Urology, Medical University of Warsaw, Lindleya 4, 02-013 Warsaw, Poland.
Biomed Res Int. 2020 Dec 12;2020:6632359. doi: 10.1155/2020/6632359. eCollection 2020.
Bladder outlet obstruction (BOO) occurs in more than 20 percent of the adult population and may lead to changes in the structure and function of the bladder. The main objective of the study was to evaluate the expression of Toll-like receptor 4 (TLR 4) and Toll-like receptor 9 (TLR 9) in the animal model of BOO as potential triggers of the inflammation phase in the bladder. In addition, the modulating effect of alpha-1 adrenergic antagonist (tamsulosin) on TLR 4 and TLR 9 expression and inflammatory markers was assessed. . Thirty-two male, 9-week-old Sprague Dawley rats were randomly divided into 4 groups: SOP-sham-operated rats with a placebo (water); SOB-sham-operated rats with an alpha-1 adrenergic antagonist; BOOP-rats with BOO and a placebo; and BOOB-rats with BOO and an alpha-1 adrenergic antagonist. The rats were given a placebo or alpha-1 adrenergic antagonist for 15 days. Next, urine and the bladder were collected from the rats for histopathological and biochemical study.
Histopathological analysis showed chronic inflammation without acute inflammation in the bladder. TLR 4 showed positive cytoplasmic reactivity in the urothelium and the smooth muscles of the bladder. TLR 9 showed positive cytoplasmic reactivity only in the urothelium. BOO caused an increase in TLR 4 and TLR 9 expression. Furthermore, treatment with an alpha-1 adrenergic antagonist had no significant effect on TLR 4 and TLR 9 expression in rats with BOO. BOO caused a significant increase in urine concentration of interleukin 6 (IL-6), while alpha-1 antagonist reduced the urine concentration of IL-6 and the concentration of interleukin 18 (IL-18).
The results suggest the participation of TLR 4 and TLR 9 receptors in the induction of inflammation in the bladder, which is the first phase in the development of pathophysiological changes in BOO.
膀胱出口梗阻(BOO)发生于超过 20%的成年人群,可能导致膀胱结构和功能发生改变。本研究的主要目的是评估 Toll 样受体 4(TLR 4)和 Toll 样受体 9(TLR 9)在 BOO 动物模型中的表达,以探究其是否为膀胱炎症阶段的潜在触发因素。此外,还评估了 α-1 肾上腺素能拮抗剂(坦索罗辛)对 TLR 4 和 TLR 9 表达及炎症标志物的调节作用。32 只 9 周龄雄性 Sprague Dawley 大鼠被随机分为 4 组:SOP-假手术对照大鼠,给予安慰剂(水);SOB-假手术对照大鼠,给予 α-1 肾上腺素能拮抗剂;BOOP-BOO 大鼠,给予安慰剂;BOOB-BOO 大鼠,给予 α-1 肾上腺素能拮抗剂。大鼠接受安慰剂或 α-1 肾上腺素能拮抗剂治疗 15 天。随后,收集大鼠尿液和膀胱进行组织病理学和生物化学研究。结果:组织病理学分析显示,膀胱存在慢性炎症而无急性炎症。TLR 4 在膀胱的尿路上皮和平滑肌中呈阳性细胞质反应。TLR 9 仅在尿路上皮中呈阳性细胞质反应。BOO 导致 TLR 4 和 TLR 9 表达增加。此外,在 BOO 大鼠中,α-1 肾上腺素能拮抗剂治疗对 TLR 4 和 TLR 9 表达无显著影响。BOO 导致尿液白细胞介素 6(IL-6)浓度显著增加,而 α-1 拮抗剂降低了尿液 IL-6 和白细胞介素 18(IL-18)的浓度。结论:结果表明 TLR 4 和 TLR 9 受体参与了膀胱炎症的诱导,这是 BOO 病理生理改变发展的第一阶段。