Departments of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
Department of Urology, Yale School of Medicine, New Haven, Connecticut.
Neurourol Urodyn. 2018 Nov;37(8):2398-2405. doi: 10.1002/nau.23592. Epub 2018 Apr 23.
Symptoms from overactive bladder (OAB) and cystitis secondary to urinary tract infection (UTI) can be similar in post-menopausal women. Effects of ovariectomy (OVX) on voiding behavior after lipopolysaccharide (LPS) intravesical exposure (surrogate for cystitis) in mice were measured. Urothelial genes associated with micturition changes were identified.
Female C57BL6/J mice underwent OVX or sham surgeries (n = 10 for each). Voiding spot assays (VSA) were performed prior to surgery, 4 weeks post-surgery, and each time after 3 consecutive days of transurethral instillation of LPS. In another experiment, mice underwent either sham (n = 9) or OVX (n = 9) surgeries. Urothelial RNAs were collected 4 weeks post-surgery, day 1 and day 3 after LPS instillation. Mouse Gene 2.0 ST Arrays (entire 34 K transcripts) were used for microarray hybridization. A set of criteria was utilized to identify gene expression changes that mimicked voiding behavior changes.
Three days after LPS exposure, OVX mice persisted with overactive whereas sham mice normalized voiding behavior. Nine urothelial paralleling voiding behavior changes were identified: IL6 (interleukin 6), IL6rα (Interleukin 6 receptor α), Ptgs2 (Prostaglandin-endoperoxide synthase 2 or COX-2), Ereg (epiregulin), Dusp6 (dual specificity phosphatase 6), Zfp948 (zinc finger protein 948), Zfp52 (Zinc finger protein 52), Gch1 (GTP cyclohydrolase 1), and Amd (S-adenosylmethionine decarboxylase). Three other genes, coding unknown proteins, were also identified: GM12840, GM23134, and GM26809.
OVX mice persisted with increased voiding frequency after LPS. Urothelial genes that could mediate this voiding behavior include IL6, COX-2, and S-adenosylmethionine decarboxylase.
在绝经后妇女中，膀胱过度活动症（OAB）和下尿路感染（UTI）继发膀胱炎的症状可能相似。本研究旨在测量脂多糖（LPS）膀胱内暴露（膀胱炎替代物）后卵巢切除术（OVX）对小鼠排尿行为的影响，并鉴定与排尿变化相关的尿路上皮基因。
雌性 C57BL6/J 小鼠接受 OVX 或假手术（每组各 10 只）。在手术前、手术后 4 周以及连续 3 天经尿道内给予 LPS 后，进行排尿点分析（VSA）。在另一项实验中，小鼠接受假手术（n=9）或 OVX（n=9）手术。手术后 4 周、LPS 灌注后第 1 天和第 3 天收集尿路上皮 RNA。使用小鼠基因 2.0 ST 微阵列（整个 34K 转录本）进行微阵列杂交。采用一组标准来鉴定与排尿行为变化相似的基因表达变化。
在 LPS 暴露后 3 天，OVX 小鼠持续表现出过度活跃，而假手术小鼠则使排尿行为恢复正常。鉴定出 9 个与排尿行为变化平行的尿路上皮基因：白细胞介素 6（IL6）、白细胞介素 6 受体α（IL6rα）、前列腺素内过氧化物合酶 2（Prostaglandin-endoperoxide synthase 2 或 COX-2）、表皮调节因子（epiregulin）、双重特异性磷酸酶 6（Dual specificity phosphatase 6）、锌指蛋白 948（zinc finger protein 948）、锌指蛋白 52（Zinc finger protein 52）、GTP 环水解酶 1（GTP cyclohydrolase 1）和 S-腺苷甲硫氨酸脱羧酶（S-adenosylmethionine decarboxylase）。还鉴定出另外 3 个编码未知蛋白的基因：GM12840、GM23134 和 GM26809。
OVX 小鼠在 LPS 后持续增加排尿频率。可能介导这种排尿行为的尿路上皮基因包括白细胞介素 6、COX-2 和 S-腺苷甲硫氨酸脱羧酶。
