利用小鼠模式評估長期注射K他命對膀胱纖維化之影響
沈正煌1、王守玠2、王守琮3,4、林淑美4、吳建德5、林昌德1、劉怡文3
1嘉義基督教醫院泌尿外科, 5病理科; 2光田綜合醫院腎臟科; 3國立嘉義大學微生物免疫與生物藥學系, 4食品科學系
Evaluation of urinary bladder fibrogenesis in mouse model of long-term ketamine injection
Cheng-Huang Shen1, Shou-Chieh Wang2, Shou-Tsung Wang3,4, Shu-Mei Lin4, Jiann-Der Wu5, Chang-Te Lin1 and Yi-Wen Liu3
1Department of Urology, Chiayi Christian Hospital, Chiayi, Taiwan; 2Division of Nephrology, Department of Internal Medicine, Kuang Tien General Hospital, Taichung, Taiwan;3Department of Microbiology, Immunology and Biopharmaceuticals; 4Department of Food Science, National Chiayi University, Chiayi, Taiwan; 5Department of Pathology, Chiayi Christian Hospital, Chiayi, Taiwan
Purpose: Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction is still not clear. This present study was to investigate the physiological and histological changes on ketamine-associated cystitis (KC) in a mouse model.
Materials and Methods: Both male and female Balb/c mice were separately distributed into the control (normal saline) and ketamine groups which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by GC-MS to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and HE stain.
Results: The voiding interval was decreased at the male mice group after 20-week ketamine administration. Moreover, the result of cDNA array analysis revealed a number of gene expressions involved in chronic wound healing response and collagen accumulation, which were closely related to fibrosis progression in the connective tissue. In HE stain of bladder tissue, the ketamine-injected mice showed prominently denser blood vessel distribution in the submucosal layer.
Conclusions: Based on the evidence in our experiment, we may build up a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse.