槲皮素调控JAK2-STAT3信号通路对压力性尿失禁模型大鼠盆底功能恢复的影响及作用机制OA

Objective To investigate the effect and mechanism of quercetin on the recovery of pelvic floor function in a rat model of stress urinary incontinence(SUI)by regulating the Janus kinase 2(JAK2)-signal transducer and activator of transcription 3(STAT3)pathway.Methods Female SD rats were selected and assigned into the control(NC)group,SUI group,low-,medium-,and high-dose quercetin(L,M,H-quercetin)groups,and H-quercetin+JAK2-STAT3 activator RO8191(H-quercetin+RO8191)group according to the criteria of 12 rats in each group.Each administration group was administered daily according to the dose,for 5 consecutive weeks.Subsequently,the urodynamics,intravesical pressure,pelvic floor function-related parameters of rats and the surface electrical signals of pelvic floor muscles were detected.The oxidative stress indexes were detected by ELISA and DCFH-DA fluorescent probe.HE staining was used to observe the pathological changes of urethral tissue.Moreover,protein expression was detected by Western blot.Results In the SUI group,the density of cells and cell nuclei in the rat urethral tissue decreased,the cells atrophied and were arranged in a disordered manner with uneven staining,the muscular layer became thinner,the interstitial spaces widened,and intracellular vacuolation was observed.The urinary leakage point pressure,maximum volume,abdominal pressure,urinary leakage point pressure when abdominal pressing,urination time interval,urination efficiency,vaginal systolic pressure,vaginal resting pressure,type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials,supeioxide dismucase(SOD)and glutathione peroxidase(GSH-Px)in the SUI group were lower than those in the NC group,while the residual urine volume,urine output,bladder neck range of motion,urethral rotation angle,malondialdhyde(MDA),reactive oxygen species(ROS)fluorescence intensities,p-JAK2/JAK2,and p-STAT3/STAT3 were higher(P＜0.05).The urinary leakage point pressure,maximum volume,abdominal pressure,urinary leakage point pressure when abdominal pressing,urination time interval,urination efficiency,vaginal systolic pressure,vaginal resting pressure,type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials,SOD and GSH-Px in the L,M,and H-quercetin groups were higher than those in the SUI group,while the residual urine volume,urine output,bladder neck range of motion,urethral rotation angle,MDA,ROS fluorescence intensities,p-JAK2/JAK2,and p-STAT3/STAT3 were lower(P＜0.05).The urinary leakage point pressure,maximum volume,abdominal pressure,urinary leakage point pressure when abdominal pressing,urination time interval,urination efficiency,vaginal systolic pressure,vaginal resting pressure,type Ⅰ and type Ⅱ pelvic floor muscle fiber potentials,SOD and GSH-Px in the H-quercetin+RO8191 group were lower than those in the H-quercetin group,while the residual urine volume,urine output,bladder neck range of motion,urethral rotation angle,MDA,ROS fluorescence intensities,p-JAK2/JAK2,and p-STAT3/STAT3 were higher(P＜0.05).Conclusion Quercetin may restore pelvic floor function in SUI rats by inhibiting the JAK2-STAT3 pathway.