Basic Research - Neurourology & LUTS/BPH & Others(구연) (E-034)

신경인성방광 모델 백서에서 Galectin-3 억제와 항콜린제 병합 요법의 효과
연세대학교 의과대학 비뇨의학교실
김상운, 성형경, 이용승, 한상원
Purpose
Galectin-3 is a protein with important biological functions, especially fibrosis formation, and as such
is currently explored as a potential target for therapy in cardiac disease. We investigate the effects of combined therapy with an anticholinergic agent and galectin-3 inhibitor on bladder dysfunction and fibrosis-related molecule expression in rats with spinal cord injury (SCI)
Methods
The spinal cord was transected at the level of T8-9 in female Sprague-Dawley rats (200-250g), which were divided into four groups; A: 6 control rats, B: 6 rat of SCI with vehicle, C: 6 rats of SCI with imidafenacin (1.57μmol/kg/day, 6.26 μmol/kg/day), D: 6 rats of SCI with combined treatment of imidafenacin and galectin-3 inhibitor (modified citrus pectin, MCP). MCP was orally administered (2ml/kg/day) after spinal cord transection. Cystometry was conducted 4 weeks after SCI in each group. We evaluated cystometric parameters and bladder tissue remodeling factors.
Results
Bladder compliance was significantly decreased in Group B while all two treatment groups (C and D) demonstrated an increased compliance, which was more obvious in group D. Non-voiding contractions (NVCs) during the storage phase of cystometry tended to be increased in group B, and it was decreased only with combination treatment of anticholinergics and MCP (group D). Post void residual was significantly increased after SCI combined with decompensated increase of bladder capacity. Reduction of post void residual was seen in both treatment groups, which was more pronounced in Group D.
In two treatment groups with SCI (C and D), the expression of galectin-3 and other fibrosis markers (a-SMA, collagen III) was decreased compared to group B. In group D, the reduction of AKT and ERK signaling pathway was demonstrated with a decrease of TGF-b.
Conclusion
The combination therapy of galectin-3 inhibitor and an anticholinergic agent increased bladder compliance, reduced NVCs and post void residual more effectively than the monotherapy of anticholinergic agent in SCI rats. Thus, the combination therapy could be applied for the treatment of neurogenic bladder dysfunction including bladder remodeling.
keywords : Neurogenic bladder, Galectin

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