[Therapeutic mechanism of Astragalus polysaccharides in bladder dysfunction in DBA mice based on regulatory role of myosin Va in neurotransmission].

This study aimed to investigate the therapeutic mechanism of Astragalus polysaccharides(APS) in improving bladder function in DBA mice by focusing on the repair of neurotransmission processes via the myosin Va pathway, specifically addressing its role in transport and docking of neurotransmitter vesicles. DBA mice were used to assess bladder dysfunction based on metabolic cage monitoring and urodynamics. The experiment included a control group, a DBA group, APS low-, medium-, and high-dose(0.256, 0.513, and 1.026 g·kg~(-1)) groups, and a positive control mecobalamin(0.195 g·kg~(-1)) group. After 3 weeks of administration, in vitro bladder detrusor muscle tension, voiding monitoring, and urodynamic assessment were performed. The expression of myosin Va and the synaptic vesicle marker protein synaptophysin was detected by RT-qPCR and immunofluorescence to further investigate the regulation of myosin Va and synaptophysin by APS. Bladder function was evaluated by in vitro detrusor tension experiments and urodynamics. The results showed that compared with the control group, the mRNA and protein expression levels of myosin Va and synaptophysin in the bladder of DBA mice were significantly decreased, suggesting that insufficient myosin Va expression led to impaired short-distance transport of vesicles. DBA mice displayed bladder contractile dysfunction, with significantly reduced contractile force upon electrical field stimulation; decreased voiding frequency and reduced voided volume; and urodynamic manifestations including prolonged voiding time, increased maximum bladder capacity, and markedly decreased maximum voiding pressure. APS treatment significantly improved bladder function in DBA mice by increasing voiding frequency, enhancing detrusor contractility, reducing residual urine volume, decreasing compliance, and significantly upregulating the mRNA and protein expression of myosin Va and synaptophysin. In conclusion, the expression of myosin Va and synaptic vesicle marker proteins in the bladder of DBA mice was significantly downregulated, which may lead to impaired neurotransmitter vesicle transport and docking, subsequently causing voiding dysfunction characterized by decreased maximum voiding pressure. APS can significantly upregulate the expression of myosin Va and synaptophysin, repair neurotransmission, thereby enhancing detrusor contractility and improving bladder function.