Li Haozhen, Li Kaixuan, Zhu Quan, Tang Zhengyan, Wang Zhao
Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Urology, The second hospital of Dalian medical university, Dalian, Liaoning, China.
Neurourol Urodyn. 2022 Mar;41(3):765-776. doi: 10.1002/nau.24892. Epub 2022 Feb 16.
Ketamine-induced cystitis (KIC) is a disease caused by ketamine that can cause lower urinary tract symptoms (LUTS). Its end-stage is bladder contracture, which is related to bladder fibrosis and poses a serious burden to patient lives.
We established a KIC model in female Sprague Dawley rats and verified bladder fibrosis in the model by Masson trichrome staining and western blot analysis. The bladders of the rats from the ketamine and control groups were used to perform transcriptome analysis. In particular, association analysis with metabolomics was also used to determine the potential mechanisms of ketamine-induced bladder fibrosis.
A total of 685 differentially expressed messenger RNAs, 71 differentially expressed long noncoding RNAs, 23 differentially expressed microRNAs, and 68 differentially expressed circular RNAs were identified. We found that ribosome, Wnt signaling, vascular endothelial growth factor signaling, cytoskeleton organization, and cytoskeletal protein binding may be potential pathways in ketamine-induced bladder fibrosis as identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. In addition, the mitogen-activated protein kinase pathway appeared to be closely related to the development of ketamine-induced bladder fibrosis according to association analysis.
In this study, using transcriptomic and correlation analyses of metabolomics, we identified pathways that may be potential targets for the prevention and treatment of ketamine-induced bladder fibrosis.
氯胺酮诱发的膀胱炎（KIC）是一种由氯胺酮引起的疾病，可导致下尿路症状（LUTS）。其终末期为膀胱挛缩，与膀胱纤维化有关，给患者生活带来严重负担。
我们在雌性Sprague Dawley大鼠中建立了KIC模型，并通过Masson三色染色和蛋白质印迹分析验证了模型中的膀胱纤维化。使用氯胺酮组和对照组大鼠的膀胱进行转录组分析。特别是，还使用了与代谢组学的关联分析来确定氯胺酮诱发膀胱纤维化的潜在机制。
共鉴定出685个差异表达的信使RNA、71个差异表达的长链非编码RNA、23个差异表达的微小RNA和68个差异表达的环状RNA。通过基因本体论和京都基因与基因组百科全书分析，我们发现核糖体、Wnt信号传导、血管内皮生长因子信号传导、细胞骨架组织和细胞骨架蛋白结合可能是氯胺酮诱发膀胱纤维化的潜在途径。此外，根据关联分析，丝裂原活化蛋白激酶途径似乎与氯胺酮诱发膀胱纤维化的发展密切相关。
在本研究中，通过转录组学和代谢组学的相关性分析，我们确定了可能成为预防和治疗氯胺酮诱发膀胱纤维化潜在靶点的途径。
