Objective To investigate the effects of mirabegron combined with electroacupuncture on urodynamic parameters in rats with overactive bladder (OAB) by regulating the insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling pathway.
Methods Sixty female SD rats were selected as the study subjects and randomly divided into control group, model group, mirabegron group, electroacupuncture group, and mirabegron+electroacupuncture group using a random number table method, with 12 rats in each group. Except for the control group, the other groups were used to establish OAB rat models by the bladder outlet obstruction method. The mirabegron group received intragastric administration of 8 mg/kg mirabegron suspension. The electroacupuncture group received electroacupuncture stimulation for 5 min each time. The mirabegron+electroacupuncture group received intragastric administration of mirabegron suspension while undergoing electroacupuncture stimulation. The control group, the model group, and the electroacupuncture group received an equal volume of normal saline intragastrically once a day for 7 consecutive days. Urodynamic parameters (basal micturition pressure, peak micturition pressure, micturition interval, and residual urine volume) were measured in each group. After measuring bladder blood flow using a laser speckle imaging instrument, the wet weight of the rat bladder tissue was weighed, and the bladder index was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of urinary nerve growth factor (NGF), and interleukin-1β (IL-1β), malondialdehyde (MDA), and superoxide dismutase (SOD) in bladder tissue. Western blot was used to detect the expression levels of phosphorylated (p)-IRS1, p-PI3K, p-AKT and p-eNOS in bladder tissue.
Results Compared with the model group, the basal micturition pressure, peak micturition pressure, and bladder index were all decreased, the residual urine volume was reduced, the micturition interval was prolonged, the bladder blood flow was increased, the SOD content in bladder tissue was increased, the NGF content in urine and the IL-1β and MDA contents in bladder tissue were decreased, and the expression levels of p-IRS1, p-PI3K, p-AKT and p-eNOS were increased in the mirabegron group, the electroacupuncture group, and the mirabegron+electroacupuncture group, with statistically significant differences (P < 0.05 or P < 0.01). The results of the above indicators in the mirabegron+electroacupuncture group were all better than those in the mirabegron group and the electroacupuncture group, with statistically significant differences (P < 0.05 or P < 0.01).
Conclusion Mirabegron combined with electroacupuncture can improve urodynamic parameters in OAB rats than used alone, and its mechanism may be related to the activation of the IRS/PI3K/AKT/eNOS signaling pathway.
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