膀胱內灌注鈣離子依存性氯離子通道抑制劑對cyclophosphamide誘發之膀胱過動症的影響--老鼠的活體研究

郭育成、張宏江¹、謝汝敦¹

臺北市立聯合醫院泌尿科；¹國立台灣大學附設醫院泌尿部

The effect of intravesical instillation of calcium-activated chloride channel blockers on cyclophosphamide-induced overactive bladder--an in vivo study in rats.

Yuh-Chen Kuo, Hong-Chiang Chang¹, Ju-Ton Hsieh¹

Department of Urology, Taipei City Hospital, Taipei, Taiwan;

Department of Urology¹, National Taiwan University Hospital, Taipei, Taiwan

Purpose: We investigated the effect of intravesical instillation of various calcium activated chloride channel (CaCC) on voiding function evaluated by continuous infusion cystometry (CMG) in anesthetic cyclophosphamide (CYP)-induced overactive bladder (OAB) rats.

Materials and Methods: A total of 64 adult male Sprague-Dawley rats (10–12 weeks) were divided into two groups (CYP-OAB and control). CYP-induced OAB was provoked by four i.p injections in 7 days (CYP-OAB: 80 mg/kg and control: saline). Continuous infusion cystometry (CMG) was performed under anesthesia to record the basal pressure, maximum bladder voiding pressure (MBVP), intercontraction interval (ICI) and episodes of spontaneous contraction. At the end of baseline CMG, the infused physiological saline solution (PSS) was replaced by one CaCC blocker solution for 30 minutes. Then the infusion solution was replaced again by the same reagent at a higher concentration for another 30 minutes. This protocol was repeated with a concentration from 10^-6M to 10^-1M (niflumic acid, NFA and 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, DIDS) or 10^-7M to 10^-2M (T16inh-A01 and N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, MONNA) to construct the concentration-response curve of each CMG parameter and determine the inhibitory concentration 50 (IC50) of every reagent (N=8 for each reagent).

Results: The increased basal pressure in OAB group could be significantly ameliorated by intravesical administration of NFA (≧1X10-3M), DIDS (≧1X10-4M), T16inh-A01 (≧1X10-5M) and MONNA (≧1X10-4M) in a concentration dependent manner. The reduced MBVP in OAB group could also be significantly recovered by intravesical treatment of NFA (≧1X10-3M), DIDS (≧1X10-4M), T16inh-A01(≧1X10-5M) and MONNA (≧1X10-5M) in a concentration dependent manner. The shortened ICI in OAB rats could be significantly lengthened by intravesical infusion of NFA (≧1X10-5M), DIDS (≧1X10-5M), T16inh-A01 (≧1X10-6M) and MONNA (≧1X10-6M) in a concentration dependent manner. The increased episodes of spontaneous contraction in OAB rats could be significantly normalized by intravesical infusion of NFA (≧1X10-2M), DIDS (≧1X10-3M), T16inh-A01 (≧1X10-5M) and MONNA (≧1X10-5M) in a concentration dependent manner. On the contrary, intravesical administration of CaCC blockers via replacement of infused PSS solution could not interfere with the CMG parameters in control group.

Conclusions: According to the results in this study, the characteristic change of CMG parameters in OAB rats could be "reversed" by intravesical administration of different CaCC blockers in OAB but not control rats, showing the potential therapeutic ability of reagents acting on CaCC.