Induction of detrusor underactivity by extensive vascular endothelial damages of iliac arteries in a rat model and its pathophysiology in the genetic levels.
Myong KimHwan Yeul YuHyein JuJung Hyun ShinAram KimJaehoon LeeChae-Min RyuHongDuck YunSeungun LeeJisun LimJinbeom HeoDong-Myung ShinMyung-Soo ChooPublished in: Scientific reports (2019)
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.
Keyphrases
- artificial intelligence
- genome wide
- oxidative stress
- spinal cord injury
- dna methylation
- diabetic rats
- high glucose
- machine learning
- copy number
- physical activity
- endothelial cells
- genome wide identification
- deep learning
- skeletal muscle
- weight loss
- drug induced
- gene expression
- poor prognosis
- multiple sclerosis
- clinical trial
- signaling pathway
- endoplasmic reticulum stress
- urinary tract
- cell cycle arrest
- epithelial mesenchymal transition
- single cell
- endovascular treatment
- preterm birth