Department of Urology, Dartmouth-Hitchcock, 1 Medical Center Dr, Lebanon, NH, USA.
Department of Molecular and Systems Biology, Geisel School of Medicine At Dartmouth and Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH, USA.
World J Urol. 2021 Jun;39(6):2197-2204. doi: 10.1007/s00345-020-03365-y. Epub 2020 Jul 21.
The impact of onabotulinum toxin type A (BoNT-A) on bladder afferent nerve pathways and chemosensory functions is an active area of investigation. There may be a role for BoNT-A in disorders of the ureter; however, no histologic studies have assessed the effects of BoNT-A on ureteral tissue. Our objective was to develop an animal model of ureteral inflammation and determine the impact of ureteral BoNT-A instillation on known mechanisms of inflammation.
The safety and feasibility of a novel animal model of ureteral inflammation was assessed. Through open cystotomy, the effect of ureteral BoNT-A instillation on inflammation was determined through H&E, masson's trichrome, Ki-67 stain, and prostaglandin E (PGE) synthase expression, a known marker of pain and inflammation in ureteral tissue. Urothelial microstructure was assessed using electron microscopy and standard histologic techniques.
All experiments were carried to completion, and no systemic signs of botulinum toxicity were seen. BoNT-A exposure was associated with a decrease in PGE synthase expression in a dose-dependent fashion. BoNT-A exposure was not found to impact collagen deposition or cell proliferation. Disruption of tight junctions between urothelial cells was observed under conditions of inflammation.
We describe the feasibility of a novel in vivo model of ureteral inflammation and report the first histologic study of the effects of BoNT-A on the ureter. Preliminary findings show that BoNT-A attenuates ureteral PGE synthase expression under conditions of inflammation. The application of BoNT-A may provide anti-inflammatory and analgesic effects in the context of ureteral disorders.
肉毒毒素 A（BoNT-A）对膀胱传入神经通路和化学感觉功能的影响是一个活跃的研究领域。BoNT-A 可能在输尿管疾病中发挥作用；然而，尚无组织学研究评估 BoNT-A 对输尿管组织的影响。我们的目的是开发一种输尿管炎症的动物模型，并确定输尿管内 BoNT-A 灌注对炎症已知机制的影响。
评估了一种新的输尿管炎症动物模型的安全性和可行性。通过开放性膀胱切开术，通过 H&E、马松三色染色、Ki-67 染色和前列腺素 E（PGE）合酶表达来确定输尿管 BoNT-A 灌注对炎症的影响，PGE 合酶表达是输尿管组织中疼痛和炎症的已知标志物。使用电子显微镜和标准组织学技术评估尿路上皮的微观结构。
所有实验均完成，未出现肉毒中毒的全身征象。BoNT-A 暴露与 PGE 合酶表达呈剂量依赖性降低有关。BoNT-A 暴露未发现影响胶原沉积或细胞增殖。在炎症条件下观察到尿路上皮细胞之间紧密连接的破坏。
我们描述了一种新的输尿管炎症体内模型的可行性，并报告了 BoNT-A 对输尿管影响的首次组织学研究。初步发现表明，BoNT-A 在炎症条件下可减弱输尿管 PGE 合酶的表达。BoNT-A 的应用可能在输尿管疾病的背景下提供抗炎和镇痛作用。
