School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Phytomedicine. 2022 Sep;104:154265. doi: 10.1016/j.phymed.2022.154265. Epub 2022 Jun 15.
Ancient prescriptions of Suo Quan Wan (SQW) have therapeutic effects on diabetic bladder dysfunction. However, the underlying mechanism remains unclear. Here, we hypothesized that SQW ameliorates bladder overactivity and regulates neurotransmission via regulating Myosin Va protein expression.
After diabetic rats were induced by streptozotocin (65 mg/kg), the model of diabetic bladder dysfunction was established by detecting fasting blood glucose, urodynamic test, in vitro muscle strip experiments, and histological examination. One week after induction, SQW was given to observe the therapeutic effect. The expression levels of Myosin Va in control, Model, SQW L and SQW H groups were detected by RT-qPCR, RNAscope and immunofluorescence assay. The expression levels of ChAT, SP, nNOS and VIP proteins were observed by immunofluorescence assay. After knockdown and overexpression of Myosin Va, the expression changes of ChAT, SP, nNOS and VIP and the regulatory role of SQW were observed.
STZ-induced DM rats had significantly higher serum glucose levels and lower body weight. Compared with the diabetic rats, SQW treatment significantly improved urination function with decreased residual volume (RV), bladder compliance (BC), non-voiding contractions (NVCs), and increased voided efficiency (VE). In addition, contractile responses of muscle strips to electrical-field stimulation (EFS), carbachol (CCh), KCl were significantly lower in the SQW H and SQW L groups than those in the model group. RT-qPCR found that the expression of Myosin Va in the bladder tissue or bladder neurons in model group was significantly increased compared with the control group, and SQW treatment significantly decreased the levels of Myosin Va. In DM rats, ChAT and SP expression were significantly increased, while nNOS and VIP expression were significantly decreased, and SQW improved this phenomenon. Interestingly, SQW ameliorated the abnormal expression of ChAT, SP, nNOS and VIP caused by myosin Va knockdown, and Myosin Va overexpression results are consistent with these.
SQW ameliorates overactive bladder and regulate neurotransmission via regulating Myosin Va mRNA and protein expression.
苏全完(SQW)古方对糖尿病膀胱功能障碍具有治疗作用。然而,其潜在机制尚不清楚。在这里,我们假设 SQW 通过调节肌球蛋白 Va 蛋白表达来改善膀胱过度活动并调节神经递质传递。
链脲佐菌素(65mg/kg)诱导糖尿病大鼠后,通过检测空腹血糖、尿动力学试验、体外肌条试验和组织学检查,建立糖尿病膀胱功能障碍模型。诱导后 1 周给予 SQW 观察治疗效果。通过 RT-qPCR、RNAscope 和免疫荧光法检测对照组、模型组、SQW L 和 SQW H 组中肌球蛋白 Va 的表达水平。通过免疫荧光法观察 ChAT、SP、nNOS 和 VIP 蛋白的表达。在敲低和过表达肌球蛋白 Va 后,观察 ChAT、SP、nNOS 和 VIP 的表达变化以及 SQW 的调节作用。
STZ 诱导的 DM 大鼠血糖明显升高,体重明显下降。与糖尿病大鼠相比,SQW 治疗可显著改善排尿功能,降低残余尿量(RV)、膀胱顺应性(BC)、非排尿收缩(NVC),并提高排尿效率(VE)。此外,SQW H 和 SQW L 组的电刺激(EFS)、卡巴胆碱(CCh)、KCl 引起的肌条收缩反应明显低于模型组。RT-qPCR 发现模型组膀胱组织或膀胱神经元中肌球蛋白 Va 的表达明显高于对照组,SQW 治疗可显著降低肌球蛋白 Va 的水平。在 DM 大鼠中,ChAT 和 SP 的表达明显增加,而 nNOS 和 VIP 的表达明显减少,SQW 改善了这种现象。有趣的是,SQW 改善了肌球蛋白 Va 敲低引起的 ChAT、SP、nNOS 和 VIP 的异常表达,而肌球蛋白 Va 过表达的结果与此一致。
SQW 通过调节肌球蛋白 Va mRNA 和蛋白表达来改善膀胱过度活动并调节神经递质传递。