| [Objective]Overactive bladder(OAB)is a common disease that affects people’s daily life.Therefore,it is of great practical significance to explore the pathogenesis of OAB and find appropriate treatment for relieve the pain of patients and improve their quality of life.The purpose of this study was to explore the role and mechanism of transient receptor potential canonical 3(TRPC3)in partial bladder outlet obstruction(pBOO)by analyzing the efficacy of common clinical treatments on bladder overactivity and establishing a mouse model of partial bladder outlet obstruction.[Methods]The therapeutic effects of different treatments were analyzed by collecting the overactive bladder syndrome score(OABSS)and the International Prostate symptom score(IPSS)of outpatients treated with different treatments.20 female ICR mice were randomly divided into experimental group and control group.The mouse OAB animal model was established by ligating the bladder outlet.Eight weeks after operation,metabolic cage voiding spot on paper(VSOP),in vitro bladder morphology analysis,bladder tissue HE staining section,detrusor strip contraction test and Western blot detection were performed to explore the role and clinical significance of TRPC3 channel in bladder hyperactivity.[Results]After receiving the corresponding treatment,the scores of OABSS problems,the total score of OABSS and the total score of IPSS were significantly improved in patients with IPSS.However,we also found that at some point in time,the corresponding score did not show significant significance compared with the baseline.In the animal experiment,two mice died in the experimental group and one mouse died in the control group,and one mouse in the control group had abnormal bladder size,so it was excluded from the statistics.Eight weeks after operation,the body weight of mice in the experimental group was(26.54±2.62g)and that in the control group was(24.84±1.76g)g,there was no significant difference between the two groups(P<0.001),but the weight and size of the bladder in the experimental group were significantly larger than those in the control group(53.16±1.79mg vs.24.54±1.80 mg,P<0.001),and the horizontal length and vertical length in the experimental group were larger than those in the control group(P<0.001).In metabolic cage study,the frequency of micturition within 12 hours in the experimental group(7.63±1.19)was significantly higher than that in the control group(4.13±0.99)(P<0.001),and the urine volume in 12 hours(1491.23 ± 94.72μL)was significantly higher than that in the control group(1344.86 ± 88.17μL).HE staining showed that the bladder wall of mice in the experimental group was significantly thickened.In the experiment of contraction of detrusor strips in vitro,the experimental group was more sensitive to carbachol,and the contractile response of mice in the experimental group was weaker than that of the control group in the electric field stimulation experiment.Nifedipine significantly inhibited the contractile response of detrusor strips during on-the-spot stimulation.[Conclusion]The clinical treatment of OAB is mainly α-receptor blockers and βadrenergic receptor agonists,these drugs can effectively improve the symptoms of patients,but can not be cured,so it is necessary to explore new treatments.We successfully established a mouse OAB model mediated by pBOO by ligating the bladder outlet.In the detrusor experiment in vitro,the detrusor of the experimental group showed irregular and spontaneous movement,and the response to carbachol was significantly enhanced,indicating that bladder outlet obstruction could improve the excitability of detrusor.But calcium channel blockers can inhibit its excitability.The expression of TRPC3 is significantly increased in the detrusor of overactive bladder,and TRPC3 may be involved in the release and development of overactive bladder.Through in-depth understanding of the relationship and mechanism between TRPC3,calcium channel and OAB,it may become a new direction in the treatment of OAB. |
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