Neurourology and urodynamics · 2020
Effects of a new β3-adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury.
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Gotoh Daisuke, Shimizu Nobutaka, Wada Naoki, Kadekawa Katsumi, Saito Tetsuichi, Mizoguchi Shinsuke, Morizawa Yosuke, Hori Shunta, Miyake Makito, Torimoto Kazumasa, de Groat William C, Fujimoto Kiyohide, Yoshimura Naoki
Аннотация
AIMS: To examine vibegron effects on lower urinary tract dysfunction (LUTD) in mice with spinal cord injury (SCI).
METHODS: Female mice underwent Th8-9 spinal cord transection and were orally administered vehicle or vibegron after SCI. We evaluated urodynamic parameters at 4 weeks after SCI with or without vibegron. Fibrosis- and ischemia-related messenger RNA (mRNA) and protein levels of collagen and elastin were measured in bladders of vehicle- and vibegron-treated SCI mice, and spinal intact mice.
RESULTS: Non-voiding contractions (NVCs) were significantly fewer (15.3 ± 8.9 vs 29.7 ± 11.4 contractions; P < .05) and the time to the first NVC was significantly longer (1488.0 ± 409.5 vs 782.7 ± 399.7 seconds; P < .01) in vibegron-treated SCI mice vs vehicle-treated SCI mice. mRNAs levels of collagen types 1 and 3, transforming growth factor-β1 (TGF-β1), and hypoxia-inducible factor-1α (HIF-1α) were significantly upregulated in vehicle-treated SCI mice compared with spinal intact and vibegron-treated SCI mice (Col 1: 3.5 vs 1.0 and 2.0-fold; P < .01 and P < .05, Col 3: 2.1 vs 1.0 and 1.2-fold; P < .01 and P < .05, TGF-β1: 1.2 vs 1.0 and 0.9-fold; P < .05 and P < .05, HIF-1α: 1.4 vs 1.0 and 1.0-fold; P < .05 and P < .01). Total collagen and elastin protein levels in vehicle- and vibegron-treated SCI mice did not differ.
CONCLUSIONS: Vibegron reduced NVCs, delayed the first NVC, and improved collagen types 1 and 3, TGF-β1, and HIF-1α mRNA expression in SCI mice. Vibegron might be effective for SCI-induced LUTD.
METHODS: Female mice underwent Th8-9 spinal cord transection and were orally administered vehicle or vibegron after SCI. We evaluated urodynamic parameters at 4 weeks after SCI with or without vibegron. Fibrosis- and ischemia-related messenger RNA (mRNA) and protein levels of collagen and elastin were measured in bladders of vehicle- and vibegron-treated SCI mice, and spinal intact mice.
RESULTS: Non-voiding contractions (NVCs) were significantly fewer (15.3 ± 8.9 vs 29.7 ± 11.4 contractions; P < .05) and the time to the first NVC was significantly longer (1488.0 ± 409.5 vs 782.7 ± 399.7 seconds; P < .01) in vibegron-treated SCI mice vs vehicle-treated SCI mice. mRNAs levels of collagen types 1 and 3, transforming growth factor-β1 (TGF-β1), and hypoxia-inducible factor-1α (HIF-1α) were significantly upregulated in vehicle-treated SCI mice compared with spinal intact and vibegron-treated SCI mice (Col 1: 3.5 vs 1.0 and 2.0-fold; P < .01 and P < .05, Col 3: 2.1 vs 1.0 and 1.2-fold; P < .01 and P < .05, TGF-β1: 1.2 vs 1.0 and 0.9-fold; P < .05 and P < .05, HIF-1α: 1.4 vs 1.0 and 1.0-fold; P < .05 and P < .01). Total collagen and elastin protein levels in vehicle- and vibegron-treated SCI mice did not differ.
CONCLUSIONS: Vibegron reduced NVCs, delayed the first NVC, and improved collagen types 1 and 3, TGF-β1, and HIF-1α mRNA expression in SCI mice. Vibegron might be effective for SCI-induced LUTD.