Ko Il Gyu, Moon Bo Min, Kim Sung Eun, Jin Jun Jang, Hwang Lakkyong, Ji Eun Sang, Kim Chang Ju, Kim Tai Hyung, Choi Hyun Hee, Chung Kyung Jin
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
Department of Urology, Gachon University Gil Medical Center, Gachon University School of Medicine, Incheon, Korea.
Int Neurourol J. 2016 Nov;20(Suppl 2):S150-158. doi: 10.5213/inj.1632768.384. Epub 2016 Nov 22.
Overactive bladder (OAB) causes urinary urgency, usually accompanied by frequency and nocturia. Alpha 1-adrenergic receptor (α-AR) antagonists are known to improve lower urinary tract symptoms associated with OAB. The α-AR antagonists constitute a variety of drugs according to the receptor subtype affinity. This study investigated the efficacy of tamsulosin, naftopidil, and a combination of the two on OAB rats.
The OAB rat model was induced by an intraperitoneal injection of cyclophosphamide for 14 days. The experimental groups were divided into 5 groups: control group, OAB-induction group, OAB-induction and tamsulosin monotherapy group, OAB-induction and naftopidil monotherapy group, and OAB-induction and tamsulosin-naftopidil combination therapy group. For the drug-treated groups, each drug was administrated for 14 days after the OAB induction. Cystometry for urodynamic evaluation and immunohistochemical stain for c-Fos and nerve growth factor (NGF) expressions in the central micturition centers were performed.
Increased contraction pressure and time with enhanced c-Fos and NGF expressions in the central micturition centers were found in the OAB rats. Tamsulosin suppressed contraction pressure and time while inhibiting c-Fos and NGF expressions. Naftopidil showed no significant effect and combination therapy showed less of an effect on contraction pressure and time. Naftopidil and combination therapy exerted no significant effect on the c-Fos and NGF expressions.
Tamsulosin showed the most prominent efficacy for the treatment of OAB compared to the naftopidil and combination. The combination of tamsulosin with naftopidil showed no synergistic effects on OAB; however, further studies of addon therapy might provide opportunities to find a new modality.
膀胱过度活动症（OAB）会导致尿急，通常伴有尿频和夜尿症。已知α1肾上腺素能受体（α-AR）拮抗剂可改善与OAB相关的下尿路症状。根据受体亚型亲和力，α-AR拮抗剂构成了多种药物。本研究调查了坦索罗辛、萘哌地尔以及二者联合用药对OAB大鼠的疗效。
通过腹腔注射环磷酰胺14天诱导建立OAB大鼠模型。将实验组分为5组：对照组、OAB诱导组、OAB诱导+坦索罗辛单药治疗组、OAB诱导+萘哌地尔单药治疗组、OAB诱导+坦索罗辛-萘哌地尔联合治疗组。对于药物治疗组，在OAB诱导后每种药物给药14天。进行膀胱测压以评估尿动力学，并对中枢排尿中枢中的c-Fos和神经生长因子（NGF）表达进行免疫组化染色。
在OAB大鼠中发现中枢排尿中枢的收缩压和时间增加，同时c-Fos和NGF表达增强。坦索罗辛可抑制收缩压和时间，同时抑制c-Fos和NGF表达。萘哌地尔无显著作用，联合治疗对收缩压和时间的作用较小。萘哌地尔和联合治疗对c-Fos和NGF表达无显著影响。
与萘哌地尔及其联合用药相比，坦索罗辛对OAB的治疗效果最为显著。坦索罗辛与萘哌地尔联合用药对OAB无协同作用；然而，进一步的附加治疗研究可能会为找到新的治疗方式提供机会。
