Division of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Sci Rep. 2018 Apr 11;8(1):5795. doi: 10.1038/s41598-018-24239-9.
Ketamine abusers may develop ulcerative cystitis and severe lower urinary tract symptoms, which is a medical dilemma. Recently, researchers have found the endemic of ketamine-induced cystitis worldwide. The intravesical administration of liposome-encapsulated onabotulinumtoxinA (Lipotoxin) might facilitate the healing of the damaged urothelium from liposomes, and reduce the urinary symptoms by onabotulinumtoxinA-induced chemo-denervation. Using female Sprague-Dawley rats, we investigated the effects of Lipotoxin on ketamine-induced cystitis. Functional magnetic resonance imaging, metabolic cage study, and cystometry were conducted. Paraffin-embedded sections were stained. The bladder mucosa and muscle proteins were assessed through Western blotting. We observed that repeated intravesical Lipotoxin instillation could improve suburothelial hemorrhage, recover the urothelial tight junction and adhesion proteins (zonula occludens-1 and E-cadherin), ensure less substance P in the urothelium, inhibit the overexpression of inflammatory mediators (IL-6, TNF-α, nuclear NF-κB, and COX-2) in the detrusor, suppress the upregulation of the mucosal TRPV1 and detrusor M-mAChR, and ameliorate bladder overactivity in the ketamine-treated rats. These data reveal the mechanisms underlying the action of Lipotoxin in ketamine-induced cystitis of rats, which provide a basis of Lipotoxin for further treating ketamine-induced cystitis in humans.
氯胺酮滥用者可能会出现溃疡性膀胱炎和严重的下尿路症状，这是一个医学难题。最近，研究人员发现了氯胺酮诱导的膀胱炎在全球范围内的流行。脂质体包裹的肉毒杆菌毒素 A（Lipotoxin）腔内给药可能通过脂质体促进受损尿路上皮的愈合，并通过肉毒杆菌毒素 A 诱导的化学去神经作用减轻尿路症状。我们使用雌性 Sprague-Dawley 大鼠研究了 Lipotoxin 对氯胺酮诱导的膀胱炎的影响。进行了功能磁共振成像、代谢笼研究和膀胱测压。对石蜡包埋切片进行染色。通过 Western blot 评估膀胱黏膜和肌肉蛋白。我们观察到，重复膀胱内 Lipotoxin 滴注可以改善黏膜下出血，恢复尿路上皮紧密连接和黏附蛋白（闭锁蛋白-1 和 E-钙黏蛋白），确保尿路上皮中 P 物质减少，抑制逼尿肌中炎症介质（IL-6、TNF-α、核 NF-κB 和 COX-2）的过度表达，抑制黏膜 TRPV1 和逼尿肌 M-型 M 受体的上调，并改善氯胺酮处理大鼠的膀胱过度活动。这些数据揭示了 Lipotoxin 在大鼠氯胺酮诱导膀胱炎中的作用机制，为 Lipotoxin 进一步治疗人类氯胺酮诱导的膀胱炎提供了依据。
