School of Forensic Medicine, China Medical University, Shenyang, China.
School of Basic Medicine, Gannan Medical University, Ganzhou, China.
Environ Toxicol. 2021 Dec;36(12):2521-2529. doi: 10.1002/tox.23365. Epub 2021 Sep 6.
Long-term ketamine abuse can cause significant lower urinary tract symptoms in humans, termed ketamine-associated cystitis (KC). Here, we established a model of long-term (6 months) ketamine administration in wild-type (C57BL/6) mice. We elucidated the pathological effects of ketamine in the bladder and investigated changes in autophagy-associated protein expression (i.e., LC3, Beclin-1, and P62) and inflammatory cytokines (i.e., IL-6 and IL-1β) in the bladder smooth muscle tissue. Long-term ketamine administration reduced the number of layers in the bladder mucosal epithelial cells (4-5 layers in the saline group vs. 2-3 layers in the ketamine groups), but increased the number of mast cells and collagen fibers. LC3-II/LC3-I, Beclin-1, IL-6, and IL-1β protein expression in the bladder smooth muscle tissues of ketamine-treated mice was significantly increased. The mRNA and protein levels of P62 in the Ket-60 mg/kg group were also significantly increased, but not the Ket-30 mg/kg group. Our results reveal that long-term ketamine administration can cause cystitis-like pathological changes in mice, and the disordered autophagy in the bladder tissue may be involved in the persistent bladder damage following long-term administration of ketamine at 60 mg/kg.
长期滥用氯胺酮可导致人类出现明显的下尿路症状，称为氯胺酮相关性膀胱炎（KC）。在这里，我们在野生型（C57BL/6）小鼠中建立了长期（6 个月）氯胺酮给药模型。我们阐明了氯胺酮在膀胱中的病理作用，并研究了自噬相关蛋白表达（即 LC3、Beclin-1 和 P62）和炎症细胞因子（即 IL-6 和 IL-1β）在膀胱平滑肌组织中的变化。长期氯胺酮给药可减少膀胱黏膜上皮细胞的层数（盐水组为 4-5 层，而氯胺酮组为 2-3 层），但增加了肥大细胞和胶原纤维的数量。氯胺酮处理小鼠膀胱平滑肌组织中 LC3-II/LC3-I、Beclin-1、IL-6 和 IL-1β蛋白表达明显增加。Ket-60mg/kg 组的 P62mRNA 和蛋白水平也明显增加，但 Ket-30mg/kg 组没有增加。我们的结果表明，长期氯胺酮给药可导致小鼠出现膀胱炎样病理变化，膀胱组织中自噬的紊乱可能与 60mg/kg 长期氯胺酮给药后持续的膀胱损伤有关。
