Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
Sci Rep. 2021 May 5;11(1):9583. doi: 10.1038/s41598-021-89089-4.
Chronic ketamine abuse is associated with bladder dysfunction and cystitis. However, the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Here, we recruited 56 ketamine abusers (KA) and 40 age-matched healthy controls (HC) and applied the iTRAQ-based proteomics approach to unravel quantitative changes in the urine proteome profile between the two groups. Many of the differentially regulated proteins are involved in the complement and coagulation cascades and/or fibrotic disease. Among them, a significant increase in APOA1 levels in KA relative to control samples (392.1 ± 59.9 ng/ml vs. 13.7 ± 32.6 ng/ml, p < 0.0001) was detected via ELISA. Moreover, urinary ketamine, norketamine and dehydronorketamine contents (measured via LC-SRM-MS) were found to be positively correlated with overactive bladder syndrome score (OABSS) and APOA1 levels with urinary RBC, WBC, OABSS and numeric pain rating scale in KA. Collectively, our results may aid in developing new molecular tool(s) for management of ketamine-induced bladder dysfunction. Moreover, information regarding the differentially regulated proteins in urine of KA provides valuable clues to establish the molecular mechanisms underlying ketamine-induced cystitis.
慢性氯胺酮滥用与膀胱功能障碍和膀胱炎有关。然而，氯胺酮滥用对尿蛋白质组谱的影响，以及尿中氯胺酮（及其代谢物）与氯胺酮诱导的膀胱功能障碍的临床病理特征之间的相关性，仍有待确定。在这里，我们招募了 56 名氯胺酮滥用者（KA）和 40 名年龄匹配的健康对照者（HC），并应用 iTRAQ 基于蛋白质组学方法来揭示两组之间尿液蛋白质组谱的定量变化。许多差异调节的蛋白质参与补体和凝血级联反应和/或纤维化疾病。其中，通过 ELISA 检测到 KA 中 APOA1 水平相对于对照样本显著增加（392.1 ± 59.9 ng/ml 比 13.7 ± 32.6 ng/ml，p < 0.0001）。此外，通过 LC-SRM-MS 测量的尿中氯胺酮、去甲氯胺酮和脱水去甲氯胺酮含量与膀胱过度活动症评分（OABSS）呈正相关，而 APOA1 水平与 KA 中的尿 RBC、WBC、OABSS 和数字疼痛评分呈正相关。总之，我们的研究结果可能有助于开发管理氯胺酮诱导的膀胱功能障碍的新分子工具。此外，KA 尿液中差异调节蛋白质的信息为建立氯胺酮诱导的膀胱炎的分子机制提供了有价值的线索。
