The aim of the present study was to investigate the association between connexin (Cx)43 levels and alterations in gap junctional mediation of intercellular communication in overactive bladder syndrome (OAB), and to examine the effects of connexin inhibitor on this condition. Adult female Wistar rats with OAB following partial bladder outlet obstruction (PBBO) (OAB group, n=37) and sham-operated rats (control group, n=17) were studied. The ultrastructure of the rat detrusor was observed by transmission electron microscopy and the protein expression levels of Cx43 were analyzed using western blot analysis. Furthermore, bladder detrusor cells in both groups were cultured and cells in the OAB group were randomly divided into ten groups. In nine of these groups, 18-β glycyrrhetinic acid (18β-GA) was administered at various doses and durations. All groups were compared using fluorescence redistribution after photobleaching and a laser scanning confocal microscope. Cystometry demonstrated that gap junctions were an abundant mechanism among adjacent cells, and Cx43 protein expression levels were increased in the OAB group following 6 weeks of obstruction, as compared with the control group. Mean fluorescence recovery rates in the OAB group were significantly increased, as compared with the control group (P<0.01). Mean fluorescence recovery rates were noted following 18β-GA administration. These results suggested that upregulation of Cx43 induces structural and functional alterations in gap junctional intercellular communication following PBOO, and connexin inhibitors may be a novel therapeutic strategy for the clinical treatment of OAB.
Experimental and therapeutic medicine. 2016 Apr 11 [Epub]
Fenghai Zhou, Haiyuan Li, Chuan Zhou, Haidi Lv, Yulei Ma, Yangmin Wang, B O Song
Department of Urology, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu 730050, P.R. China., Department of Urology, The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730030, P.R. China., Department of Urology, West China School of Medicine, Sichuan University, Chengdu, Sichuan 610000, P.R. China., Department of Urology, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu 730050, P.R. China., Department of Urology, The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730030, P.R. China., Department of Urology, Lanzhou General Hospital, Lanzhou Command, PLA, Lanzhou, Gansu 730050, P.R. China., Department of Urology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.