目的 基于转化生长因子β1/结缔组织生长因子(TGF-β1/CTGF)信号通路探究肌源干细胞(MDSCs)对压力性尿失禁(SUI)大鼠排尿功能和尿道损伤的影响.方法 分离、培养 MDSCs,免疫细胞化学法检测 MDSCs 标志物Desmin和 Sca-1 表达.40 只 SD雌性大鼠按照随机数字表法分为 4 组:NC组(不作任何处理)、SUI 组(SUI 模型)、MDSCs组(SUI 模型+MDSCs 治疗)、MDSCs+SB431542 组(SUI 模型+MDSCs 治疗+通路抑制剂SB431542 处理),每组 10 只.比较 4 组大鼠喷嚏阳性率、尿动力学指标[膀胱最大容积(MBC)、漏尿点压(LPP)、腹压漏尿点压(ALPP)、排尿量、残余尿量、排尿效率];H E染色观察 4 组尿道组织病理学变化;蛋白免疫印迹法检测4 组尿道组织中TGF-β1、CTGF蛋白表达.结果 成功获得 Desmin和 Sca-1 均呈阳性表达的 MDSCs.与 NC 组比较,SUI组喷嚏阳性率、MBC、LPP、ALPP、排尿量、残余尿量均增加,排尿效率、TGF-β1 和 CTGF蛋白表达均降低(P<0.05),伴有严重尿道损伤;与 SUI组比较,MDSCs组喷嚏阳性率、MBC、LPP、ALPP、排尿量、残余尿量均降低,排尿效率、TGF-β1 和CTGF蛋白表达均增加(P<0.05),尿道损伤减轻;与 MDSCs组比较,MDSCs+SB431542组喷嚏阳性率、MBC、LPP、ALPP、排尿量、残余尿量均增加,排尿效率、TGF-β1 和 CTGF 蛋白表达均降低(P<0.05),尿道损伤加重.结论 MDSCs 可改善 SUI 大鼠的排尿功能,减轻尿道损伤,其可能是通过调控 TGF-β1/CTGF信号通路发挥作用.
Objective To investigate the effects of muscle-derived stem cells(MDSCs)on voi-ding dysfunction and urethral injury in rats with stress urinary incontinence(SUI)based on trans-forming growth factor β1/connective tissue growth factor(TGF-β1/CTGF)signaling pathway.Methods MDSCs were isolated and cultured,and the expression of Desmin and Sca-1 were detec-ted by immunocytochemistry.A total of 40 female SD rats were randomly allocated to four groups:NC group(rats with no treatment),SUI group(rats with SUI),MDSCs group(SUI rats treated with MDSCs),and MDSCs+SB431542 group(SUI rats treated with MDSCs and TGF-β1/CTGF signaling inhibitor SB431542),with 10 rats in each group.The positive rate of sneezing test,maximum bladder volume(MBC),leak point pressure(LPP),abdominal leak point pressure(ALPP),urine output,residual urine output,and voiding efficiency were compared between the four groups.The histopathological changes of urethra were observed by HE staining,and the ex-pression of TGF-β1 and CTGF proteins in urethral tissues were detected by Western blotting.Re-sults The MDSCs with Desmin and Sca-1 expression were successfully obtained.Compared with the NC group,the SUI rats showed an increase in positive rate of sneezing test,MBC,LPP,AL-PP,urine output and residual urine output,a decrease in voiding efficiency and TGF-β1 and CTGF expression,and severe urethral injury(P<0.05).Compared with the SUI group,MDSCs reduced the positive rate of sneezing test,MBC,LPP,ALPP,urine output and residual urine output,en-hanced the voiding efficiency and TGF-β1 and CTGF expression,and relieved urethral injury(P<0.05).Compared with the MDSCs group,SB431542 treatment increased the positive rate of snee-zing test,MBC,LPP,ALPP,urine output and residual urine output,reduced the voiding efficiency and TGF-β1 and CTGF expression,and aggravated urethral injury(P<0.05).Conclusion MDSCs can improve voiding function and alleviate urethral injury in rats with SUI through regulating TGF-β1/CTGF signaling pathway.