Induction of detrusor underactivity by extensive vascular endothelial damages of iliac arteries in a rat model and its pathophysiology in the genetic levels.
Myong Kim: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. ORCID
Hwan Yeul Yu: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Hyein Ju: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Jung Hyun Shin: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Aram Kim: Department of Urology, Konkuk University Hospital, Konkuk University School of Medicine, Seoul, 05030, Republic of Korea.
Jaehoon Lee: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Chae-Min Ryu: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
HongDuck Yun: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Seungun Lee: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Jisun Lim: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Jinbeom Heo: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea.
Dong-Myung Shin: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. d0shin03@amc.seoul.kr. ORCID
Myung-Soo Choo: Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea. mschoo@amc.seoul.kr. ORCID
We tried to establish a reliable detrusor underactivity (DUA) rat model and to investigate pathophysiology of chronic bladder ischemia (CBI) on voiding behavior and bladder function. Adult male rats were divided into five groups. The arterial injury (AI) groups (AI-10, AI-20, AI-30) underwent vascular endothelial damage (VED) of bilateral iliac arteries (with 10, 20, and 30 bilateral repetitions of injury, respectively) and received a 1.25% cholesterol diet. The sham group underwent sham operation and received the same diet. Controls received a regular diet. After 8 weeks, all rats underwent unanesthetized cystometrogram. Bladder tissues were processed for organ bath investigation, immunohistochemistry staining, and genome-wide gene expression analysis. Awake cystometry analysis showed that frequency of voiding contractions and micturition pressure were lower in the AI-30 group than in sham group (p < 0.01). Contractile responses to various stimuli were lower in AI-20 and AI-30 groups (both p < 0.001). In the AI-20 and AI-30 groups, atherosclerotic occlusion in the iliac arteries, tissue inflammation, fibrosis, denervation, and apoptosis of bladder muscle were prominent compared to the sham. Mechanistically, the expression of purinergic receptor P2X-1 was reduced in the AI-30 group, and the genome-wide gene expression analysis revealed that genes related to IL-17 and HIF-1 signaling pathways including INF-γ receptor-1 and C-X-C motif chemokine ligand-2 were upregulated in the CBI-induced DUA rat model. A rat model of progressive VED successfully induced DUA. Abnormal tissue inflammation, fibrosis, denervation, and bladder muscle tissue apoptosis may be involved in CBI-induced DUA pathophysiology.
References
Int Neurourol J. 2018 Jan;22(Suppl 1):S34-45
[PMID: 29385783]
Stem Cell Reports. 2018 Feb 13;10(2):600-614
[PMID: 29307581]
