K他命誘導的膀胱功能障礙在老鼠模型中與細胞外基質積聚和鈣信號傳導損傷有關
張恩承1、沈正煌1,2、王守琮3,4、王守玠3-5、林淑美3、林瑞進6、戴元昌7、劉怡文4
1嘉義基督教醫院泌尿外科,7病理科；2亞洲大學食品營養與保健生技學系
,3國立嘉義大學食品科學系,4微生物免疫與生物藥學系,6森林暨自然資源學系；5光田綜合醫院腎臟科
Ketamine-induced bladder dysfunction is associated with extracellular matrix accumulation and impairment of calcium signaling in a mouse model
CHEONG IAN SENG1, CHENG-HUANG SHEN1,2*, SHOU-TSUNG WANG3,4*, SHOU-CHIEH WANG3-5, SHU-MEI LIN3, LEI-CHEN LIN6, YUAN-CHANG DAI7 and YI-WEN LIU4
1Department of Urology, Chiayi Christian Hospital, Chiayi, Taiwan; 2Department of Health and Nutrition Biotechnology, Asian University, Taichung, Taiwan; Departments of 3Food Science and 4Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, Taiwan; 5Division of Nephrology, Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan; 6Department of Forestry and Natural Resources, National Chiayi University, Chiayi, Taiwan; 7Department of Pathology, Chiayi Christian Hospital, Chiayi, Taiwan.
Purpose: Due to the rising abuse of ketamine usage in recent years, ketamine-induced urinary tract syndrome has received increasing attention. The present study aimed to investigate the molecular mechanism underlying ketamine-associated cystitis in a mouse model.
Materials and Methods: Female C57BL/6 mice were randomly divided into two groups: One group was treated with ketamine (100 mg/kg/day of ketamine for 20 weeks), whereas, the control group was treated with saline solution. In each group, micturition frequency and urine volume were examined to assess urinary voiding functions. Mouse bladders were extracted and samples were examined for pathological and morphological alterations using haematoxylin and eosin staining, Masson’s trichrome staining and scanning electron microscopy. A cDNA microarray was conducted to investigate the differentially expressed genes following treatment with ketamine.
Results: The results suggested that bladder hyperactivity increased in the mice treated with ketamine. Furthermore, treatment with ketamine resulted in a smooth apical epithelial surface, subepithelial vascular congestion and lymphoplasmacytic aggregation. Microarray analysis identified a number of genes involved in extracellular matrix accumulation, which is associated with connective tissue fibrosis progression, and in calcium signaling regulation, that was associated with urinary bladder smooth muscle contraction.
Conclusions: Collectively, the present results suggested that these differentially expressed genes may serve critical roles in ketamine-induced alterations of micturition patterns and urothelial pathogenesis. Furthermore, the present findings may provide a theoretical basis for the development of effective therapies to treat ketamine-induced urinary tract syndrome.