TY - JOUR
T1 - Pharmacologic and molecular characterization of underactive bladder induced by lumbar canal stenosis
AU - Wang, Hung Jen
AU - Tyagi, Pradeep
AU - Chuang, Yao Chi
AU - Yoshimura, Naoki
AU - Huang, Chao Cheng
AU - Chancellor, Michael B.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Objective To investigate the voiding function in a rat model of lumbar canal stenosis (LCS) using pharmacologic and molecular approaches. Methods Sixty-one female Sprague-Dawley rats were broadly split into a sham and an LCS group. A hole was surgically drilled in the L5-L6 epidural space and filled with a rectangular piece of silicone rubber. Metabolic cage study at week 2 and continuous cystometry (CMG) under urethane anesthesia at weeks 2 and 4 were performed. During CMG, prostaglandin E2 or sulprostone, an prostaglandin E receptor 1 and prostaglandin E receptor 3 agonist was administered locally and intravenously, respectively, and the bladder was then harvested for histology and Western blot. Results Compared with sham, the LCS group showed dribbling urination and progressive increase in bladder size. CMG under urethane anesthesia in the LCS group was marked by overflow incontinence and acontractile bladder. Administration of intravesical prostaglandin E2 (200 μM) or intravenous sulprostone (0.1 mg/kg) in the sham group induced bladder overactivity, but decreased the compliance and failed to restore the bladder emptying function in the LCS group. The LCS group showed edematous changes and muscle thinning at week 2, which were partially restored by week 4. Histologic changes were accompanied by downregulation of agrin protein (64.0%) at week 2 and upregulation of M2 receptor (65.4%) at week 4. Expression of M3, protein gene product 9.5, and nerve growth factor did not differ between groups. Conclusion LCS-induced underactive bladder is associated with altered expression of agrin and M2 receptor. The underactive bladder model is clinically relevant, and the findings indicate potential molecular targets for new therapies.
AB - Objective To investigate the voiding function in a rat model of lumbar canal stenosis (LCS) using pharmacologic and molecular approaches. Methods Sixty-one female Sprague-Dawley rats were broadly split into a sham and an LCS group. A hole was surgically drilled in the L5-L6 epidural space and filled with a rectangular piece of silicone rubber. Metabolic cage study at week 2 and continuous cystometry (CMG) under urethane anesthesia at weeks 2 and 4 were performed. During CMG, prostaglandin E2 or sulprostone, an prostaglandin E receptor 1 and prostaglandin E receptor 3 agonist was administered locally and intravenously, respectively, and the bladder was then harvested for histology and Western blot. Results Compared with sham, the LCS group showed dribbling urination and progressive increase in bladder size. CMG under urethane anesthesia in the LCS group was marked by overflow incontinence and acontractile bladder. Administration of intravesical prostaglandin E2 (200 μM) or intravenous sulprostone (0.1 mg/kg) in the sham group induced bladder overactivity, but decreased the compliance and failed to restore the bladder emptying function in the LCS group. The LCS group showed edematous changes and muscle thinning at week 2, which were partially restored by week 4. Histologic changes were accompanied by downregulation of agrin protein (64.0%) at week 2 and upregulation of M2 receptor (65.4%) at week 4. Expression of M3, protein gene product 9.5, and nerve growth factor did not differ between groups. Conclusion LCS-induced underactive bladder is associated with altered expression of agrin and M2 receptor. The underactive bladder model is clinically relevant, and the findings indicate potential molecular targets for new therapies.
UR - http://www.scopus.com/inward/record.url?scp=84931956903&partnerID=8YFLogxK
U2 - 10.1016/j.urology.2015.01.017
DO - 10.1016/j.urology.2015.01.017
M3 - 文章
C2 - 25770729
AN - SCOPUS:84931956903
SN - 0090-4295
VL - 85
SP - 1284
EP - 1290
JO - Urology
JF - Urology
IS - 6
ER -