RNA干扰降低膀胱TGF-β1表达能够改善脊髓损伤大鼠的膀胱功能和纤维化  

RNAi-reduced bladder TGF-β1 expression improves bladder function and fibrosis in rats with spinal cord injury

作　　者：贾春松[1] 赵彦坡 尚振华 邢添瑛 欧彤文[1] JIA Chun-song;ZHAO Yan-po;SHANG Zhen-hua;XING Tian-ying;OU Tong-wen(Department of Urology, Xuanwu Hospital Capital Medical University, Beijing 100053;Department of Neurology,Mentougou District Hospital, Beijing 102300, China)

机构地区：[1]首都医科大学宣武医院泌尿外科,北京100053 [2]门头沟区医院神经内科,北京102300

出　　处：《基础医学与临床》2021年第7期1007-1012,共6页Basic and Clinical Medicine

基　　金：北京市自然科学基金(7162078);北京市医院管理局临床医学发展专项经费(ZYLX201801)。

摘　　要：目的探索通过RNA干扰(RNAi)降低膀胱TGF-β1表达治疗神经源性膀胱(NB)的效果。方法将48只雌性大鼠均分为假手术组、T10脊髓横断组、LV-vector组和LV-shTGF-β1组。假手术组行T10脊髓横断假手术,其余3组行脊髓横断。术后即行膀胱壁注射,前两组为0.9%氯化钠溶液,LV-vector组为对照病毒,LV-shTGF-β1组为TGF-β1 RNAi慢病毒。术后第28天测压和称重膀胱,并将膀胱组织用HE和Masson染色,用免疫组化、RT-qPCR和Western blot检测逼尿肌TGF-β1的表达。结果与假手术组相比,其余3组逼尿肌过度活动的次数和幅度显著增加(P<0.01),膀胱容量显著减小(P<0.05),膀胱质量和逼尿肌间质含量以及TGF-β1表达显著增加(P<0.05);T10脊髓横断组与LV-vector组相比,两者各项指标差异无统计学意义;LV-shTGF-β1组与T10脊髓横断组或LV-vector组相比,其逼尿肌过度活动的次数和幅度显著减少(P<0.01),膀胱容量显著增加(P<0.01),膀胱质量和逼尿肌间质含量以及TGF-β1表达显著减少(P<0.05)。结论RNAi降低膀胱TGF-β1表达能够改善脊髓损伤大鼠的逼尿肌过度活动和膀胱纤维化。Objective To explore the effect of reducing bladder TGF-β1 expression with RNA interference(RNAi)on neurogenic bladder(NB).Methods Forty-eight female rats were evenly divided into sham,T10 transaction,LV-vector and LV-shTGF-β1 groups.The sham group underwent sham operation of T10 spinal cord transection,and the other three groups underwent spinal cord transection.The bladder wall was injected immediately after the operation.The first two groups were injected with 0.9%NaCl,the LV-vector group was the control lentivirus,and the LV-shTGF-β1 group was TGF-β1 RNAi lentivirus.On the 28th day after operation,cystometry and bladder weighing were performed,the bladder tissue was stained with HE and Masson,and the expression of detrusor TGF-β1 was detected by immunohistochemistry,RT-qPCR and Western blot.Results In the three groups with spinal cord transection compared with the sham group,the frequency and amplitude of detrusor over activity were significantly increased(P<0.01),the bladder capacity was significantly reduced(P<0.05),and the bladder weight,the detrusorinterstitial percentage and TGF-β1 expression were significantly increased(P<0.05).The T10 transection group had no significant difference compared with the LV-vector group.In the LV-shTGF-β1 group compared with the T10 transection group,the frequency and amplitude of detrusor over activity were significantly reduced(P<0.01),the bladder capacity was significantly increased(P<0.01),and the bladder weight,the detrusor interstitial percentage and TGF-β1 expression were significantly reduced(P<0.05).Conclusions Reducing bladder TGF-β1 expression with RNAi can improve detrusor over activity and bladder fibrosis in rats with spinal cord injury.

关 键 词：脊髓损伤 逼尿肌过度活动 膀胱纤维化 RNA干扰(RNAI) TGF-Β1 

分 类 号：R734.2[医药卫生—肿瘤]