Ruetten Hannah, Sandhu Simran K, Fox Olivia, Zhu Jonathan, Sandhu Jaskiran K, Vezina Chad M
University of Wisconsin-Madison/UMASS Boston/UT-Southwestern George M. O'Brien Center for Benign Urologic Research Madison, Wisconsin 53706, USA.
School of Veterinary Medicine, University of Wisconsin-Madison Madison, Wisconsin 53706, USA.
Am J Clin Exp Urol. 2023 Feb 25;11(1):59-68. eCollection 2023.
Prostatic inflammation and prostatic fibrosis are associated with lower urinary tract dysfunction in men. Prostatic inflammation arising from a transurethral uropathogenic infection is sufficient to increase prostatic collagen content in male mice. It is not known whether and how the sequence, duration and chronology of prostatic infection influence urinary function, prostatic inflammation and collagen content. We placed a transurethral catheter into adult male C57BL/6J mice to deliver uropathogenic UTI189 two-weeks prior to study endpoint (to evaluate the short-term impact of infection), 10-weeks prior to study endpoint (to evaluate the long-term impact of infection), or two-, six-, and ten-weeks prior to endpoint (to evaluate the impact of repeated intermittent infection). Mice were catheterized the same number of times across all experimental groups and instilled with sterile saline when not instilled with to control for the variable of catheterization. We measured bacterial load in free catch urine, body weight and weight of bladder and dorsal prostate; prostatic density of leukocytes, collagen and procollagen 1A1 producing cells, and urinary function. Transurethral instillation caused more severe and persistent bacteriuria in mice with a history of one or more transurethral instillations of sterile saline or . Repeated intermittent infections resulted in a greater relative bladder wet weight than single infections. However, voiding function, as measured by the void spot assay, and the density of collagen and ProCOL1A1+ cells in dorsal prostate tissue sections did not significantly differ among infection groups. The density of CD45+ leukocytes was greater in the dorsal prostate of mice infected two weeks prior to study endpoint but not in other infection groups compared to uninfected controls.
前列腺炎症和前列腺纤维化与男性下尿路功能障碍有关。经尿道尿路致病性感染引起的前列腺炎症足以增加雄性小鼠的前列腺胶原蛋白含量。目前尚不清楚前列腺感染的顺序、持续时间和时间顺序是否以及如何影响泌尿功能、前列腺炎症和胶原蛋白含量。在研究终点前两周(以评估感染的短期影响)、研究终点前十周(以评估感染的长期影响)或终点前两周、六周和十周(以评估反复间歇性感染的影响),我们将经尿道导管插入成年雄性C57BL/6J小鼠体内,以输送尿路致病性UTI189。所有实验组的小鼠导尿次数相同,在不注入UTI189时注入无菌盐水,以控制导尿变量。我们测量了自由采集尿液中的细菌载量、体重、膀胱和背侧前列腺的重量;前列腺白细胞、胶原蛋白和产生前胶原蛋白1A1的细胞的密度以及泌尿功能。经尿道注入UTI189在有一次或多次经尿道注入无菌盐水或UTI189病史的小鼠中引起更严重和持续的菌尿。反复间歇性感染导致相对膀胱湿重比单次感染更大。然而,通过排尿点试验测量的排尿功能以及背侧前列腺组织切片中胶原蛋白和ProCOL1A1+细胞的密度在感染组之间没有显著差异。与未感染的对照组相比,在研究终点前两周感染的小鼠背侧前列腺中CD45+白细胞的密度更高,但在其他感染组中则没有。