电针抑制HCN1-Cav3.1通路对神经源性膀胱大鼠尿失禁的影响OA

Objective To investigate the effects of electroacupuncture(EA)regulating HCN1-Cav3.1 pathway on urinary incontinence in rats with neurogenic bladder(NB)after suprasacral spinal cord injury(SSCI)and its mechanism.Methods Totally 44 rats were divided into sham-operation group(n=11)with random number table method,and the remaining rats were divided into model group,EA group and inhibitor group after successful SSCI modeling.The EA group received EA at the acupoints"Guanyuan","Zhongji",and bilateral"Sanyinjiao"(once a day for 10 times).The inhibitor group received intraperitoneal injection of ivabradine(10 mg/kg,once every other day,5 times in total),an inhibitor of HCN1.After the intervention,urodynamic indexes were detected,and bladder tissue morphology was observed by HE staining,the mRNA and protein expressions of HCN1 and Cav3.1 subtypes of T-type calcium channel in bladder tissue were detected by RT-qPCR and Western blot,and the positive expressions of c-Kit,HCN1 and Cav3.1 in bladder tissue were detected by immunofluorescence.Results Compared with the sham-operation group,the rats in the model group had rough fur,decreased body mass,decreased appetite,reduced water consumption,swollen bladder,urinary incontinence,increased bladder basic pressure and leak point pressure,decreased maximum bladder capacity and bladder compliance(P<0.01),and increased bladder wet weight and bladder index(P<0.01);the mucosal epithelial cells of bladder tissue were disordered,with a large number of vacuolar degeneration,destruction of lamina propria structure,loose smooth muscle layer structure and disordered fiber arrangement,more vascular bleeding and inflammatory cell infiltration were observed,the mRNA and protein expressions of HCN1 and Cav3.1 in bladder tissue increased(P<0.01),and the positive expressions of c-Kit,HCN1 and Cav3.1 increased(P<0.01).Compared with the model group,the basic pressure and leak point pressure of the bladder decreased in EA group and the inhibitor group,,the maximum bladder capacity and compliance increased(P<0.01),the morphology and structure of the bladder were relatively improved,the wet weight and bladder index decreased(P<0.01),the mRNA and protein expressions of HCN1 and Cav3.1 decreased(P<0.05,P<0.01),and the positive expressions of c-Kit,HCN1 and Cav3.1 decreased(P<0.05,P<0.01);there was no significant difference in the above indexes between the EA group and the inhibitor group(P>0.05).Conclusion EA can reduce the excitability of bladder interstitial cells of Cajal by inhibiting HCN1-Cav3.1 pathway,thereby alleviating excessive contraction of bladder detrusor and improving urinary incontinence in rats with neurogenic bladder after SSCI.