肌源干细胞通过TGF-β1/CTGF信号通路减轻压力性尿失禁大鼠的排尿障碍和尿道损伤  

Muscle-Derived Stem Cells Alleviate Voiding Dysfunction and Urethral Injury in Rats with Stress Urinary Incontinence through TGF-β1/CTGF Signaling Pathway

作　　者：李善凤[1] 龚静亚[3] 沈海川[1] 朱永贞 孙瑗 王玲 顾月 姚明莹 陈品静 LI Shan-feng;GONG Jing-ya;SHEN Hai-chuan;ZHU Yong-zhen;SUN Yuan;WANG Ling;GU Yue;YAO Ming-ying;CHEN Pin-jing(Department of Obstetrics and Gynecology,Lianyungang Maternal and Child Health Hospital,Lianyungang 222006,China;Clinical Laboratory,Lianyungang Maternal and Child Health Hospital,Lianyungang 222006,China;Department of Obstetrics and Gynecology,the Second Affiliated Hospital of Soochow University,Suzhou 215008,China;Department of Obstetrics and Gynecology,the First Health Center of Wenquan Town,Donghai County,Lianyungang 222301,China;Department of Obstetrics and Gynecology,Yishan Town Central Health Center,Guanyun County,Lianyungang 222299,China)

机构地区：[1]连云港市妇幼保健院妇产科,江苏连云港222006 [2]连云港市妇幼保健院检验科,江苏连云港222006 [3]苏州大学附属第二医院妇产科,江苏苏州215008 [4]东海县温泉镇第一卫生院妇产科,江苏连云港222301 [5]灌云县伊山镇中心卫生院妇产科,江苏连云港222299

出　　处：《南昌大学学报（医学版）》2024年第1期25-31,共7页Journal of Nanchang University：Medical Sciences

基　　金：江苏省老年健康科研项目(LK2021048);江苏省妇幼保健协会科研课题(FYX202110);连云港市卫生科技项目(202127)。

摘　　要：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];HE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 voiding dysfunction and urethral injury in rats with stress urinary incontinence(SUI)based on transforming growth factorβ1/connective tissue growth factor(TGF-β1/CTGF)signaling pathway.Methods MDSCs were isolated and cultured,and the expression of Desmin and Sca-1 were detected 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 expression of TGF-β1 and CTGF proteins in urethral tissues were detected by Western blotting.Results 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,ALPP,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,enhanced 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 sneezing 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.

关 键 词：压力性尿失禁 肌源干细胞 转化生长因子Β1 结缔组织生长因子 动物 实验 大鼠 

分 类 号：R695.1[医药卫生—泌尿科学]