Division of Urology, Department of Surgery, University of Colorado Denver School of Medicine, Aurora, CO, 80045, USA.
Department of Pediatric Urology, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR, 97239, USA.
Sci Rep. 2022 Mar 24;12(1):5113. doi: 10.1038/s41598-022-08585-3.
Vincristine (VCR) is one of the most common chemotherapy agents used in pediatric oncology. Despite the well-known VCR-induced peripheral neuropathy, potential impacts of VCR on lower urinary tract (LUT) function remain poorly defined. We investigated the effects of systemic VCR exposure in childhood on LUT function by using juvenile mice treated with VCR (4 mg/kg) or saline and evaluated at 5 weeks later. VCR induced a decreased urinary frequency with increased functional bladder capacity and non-void contractions. There were no changes in detrusor contractility between the groups. VCR exposure caused sexual dimorphic changes; in females, increased intravesical pressure at micturition and downregulations of a major player in bladder afferent firing, Htr3b, in the bladders, and Cav1.2 in the lumbosacral dorsal root ganglia (Ls-DRG), while male mice displayed increases in bladder compliance and detrusor activity, upregulations of IL-2, Trpa1 and Itga1 in the bladders and neuroinflammation-related genes, P2×4, P2×7, IL-2 and CD68 in the Ls-DRG. These results suggest that that systemic VCR exposure caused sensory neuropathy via sex-dimorphic mechanisms, leading to altered LUT function. These changes might clinically present as gender-specific signs or symptoms of LUT dysfunction, and follow-up urological assessment may be of benefit for pediatric cancer patients treated with VCR.
长春新碱（VCR）是儿科肿瘤学中最常用的化疗药物之一。尽管众所周知长春新碱会引起周围神经病变，但长春新碱对下尿路（LUT）功能的潜在影响仍未得到明确界定。我们通过使用长春新碱（4mg/kg）或生理盐水处理幼年小鼠，并在 5 周后进行评估，研究了全身性长春新碱暴露对 LUT 功能的影响。长春新碱导致尿频率降低，膀胱功能容量增加和非排空收缩。两组间逼尿肌收缩力无变化。长春新碱暴露引起性别二态性变化；在雌性中，排尿时膀胱内压增加，膀胱传入放电的主要参与者 Htr3b 和腰骶部背根神经节（Ls-DRG）中的 Cav1.2 下调，而雄性小鼠显示膀胱顺应性和逼尿肌活动增加，膀胱中 IL-2、Trpa1 和 Itga1 以及 Ls-DRG 中的神经炎症相关基因 P2×4、P2×7、IL-2 和 CD68 上调。这些结果表明，全身性长春新碱暴露通过性别二态机制引起感觉神经病变，导致 LUT 功能改变。这些变化可能会在临床上表现为 LUT 功能障碍的特定性别症状或体征，对接受长春新碱治疗的儿科癌症患者进行随访泌尿科评估可能会受益。
