Li Ning, Ding Honglin, Li Zizheng, Liu Yili, Wang Ping
Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.
Department of Urology, Affiliated Hospital, Chifeng University, 42 Wangfu Street, Chifeng, Neimeng, China.
Int Urol Nephrol. 2019 Jan;51(1):61-72. doi: 10.1007/s11255-018-2016-5. Epub 2018 Oct 25.
Obesity usually induces overactive bladder (OAB) associated with detrusor overactivity, which is related to increased contractility of the detrusor smooth muscle (DSM). Small-conductance Ca-activated K (SK) channels play a constitutive role in the regulation of DSM contractility. However, the role of SK channels in the DSM changes in obesity-related OAB is still unknown. Here, we tested the hypothesis that obesity-related OAB is associated with reduced expression and activity of SK channels in DSM and that SK channels activation is a potential treatment for OAB.
Female Sprague-Dawley rats were fed a normal diet (ND) or a high-fat diet (HFD) and weighed after 12 weeks. Urodynamic studies, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and isometric tension recording were performed.
Increased average body weights and urodynamically demonstrated OAB were observed in HFD rats. qRT-PCR experiments revealed a decrease in the mRNA expression level of SK channel in DSM tissue of the HFD rats. Isometric tension recordings indicated an attenuated relaxation effect of NS309 on the spontaneous phasic and electrical field stimulation-induced contractions that occurred via SK channel activation in HFD DSM strips.
Reduced expression and activity of SK channels in the DSM contribute to obesity-related OAB, indicating that SK channels are a potential therapeutic target for OAB.
肥胖通常会诱发与逼尿肌过度活动相关的膀胱过度活动症（OAB），这与逼尿肌平滑肌（DSM）收缩性增加有关。小电导钙激活钾（SK）通道在DSM收缩性调节中起重要作用。然而，SK通道在肥胖相关OAB中DSM变化中的作用仍不清楚。在此，我们验证了以下假设：肥胖相关OAB与DSM中SK通道的表达和活性降低有关，且激活SK通道是治疗OAB的一种潜在方法。
给雌性Sprague-Dawley大鼠喂食正常饮食（ND）或高脂饮食（HFD），12周后称重。进行尿动力学研究、定量逆转录聚合酶链反应（qRT-PCR）和等长张力记录。
在HFD大鼠中观察到平均体重增加且尿动力学显示存在OAB。qRT-PCR实验显示HFD大鼠DSM组织中SK通道的mRNA表达水平降低。等长张力记录表明，NS309对HFD大鼠DSM条带中通过SK通道激活产生的自发性相位和电场刺激诱导的收缩的舒张作用减弱。
DSM中SK通道的表达和活性降低导致肥胖相关OAB，表明SK通道是OAB的一个潜在治疗靶点。
