人脐带间充质干细胞尿道旁注射治疗大鼠压力性尿失禁  

Treatment of stress urinary incontinence in rats with umbilical cord mesenchymal stem cells

作　　者：张高娜 孟博文 徐圣龙 詹瑛[4] 张宁[4] 高群[4] 陈洁[4] 于莎[4] 王丹 王慧[4] Zhang Gaona;Meng Bowen;Xu Shenglong;Zhan Ying;Zhang Ning;Gao Qun;Chen Jie;Yu Sha;Wang Dan;Wang Hui(Qingdao University Medical College,Qingdao 266073,China;BGI Cell,BGI-Qingdao,BGI-Shenzhen,Qingdao 266555,China;Department of Obstetrics,Qingdao Women and Children’s Hospital,Qingdao 266011,China;Department of Obstetrics,the Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学医学部,青岛266073 [2]青岛中德华大细胞科技有限公司,青岛266555 [3]青岛市妇女儿童医院产科,青岛266011 [4]青岛大学附属医院产科,青岛266003

出　　处：《中华实验外科杂志》2024年第6期1189-1193,共5页Chinese Journal of Experimental Surgery

摘　　要：目的观察经尿道注射人脐带间充质干细胞(hUC-MSCs)治疗大鼠模拟分娩损伤所致压力性尿失禁(SUI),并探讨其分子机制。方法选用无特定病原体(SPF)级雌性Sprague-Dawley大鼠12只(6周龄,145~185 g),按照随机数字表法分为干细胞注射组、生理盐水注射组、空白对照组,分别为5、4、3只。干细胞注射组和生理盐水注射组使用多次阴道球囊扩张术(MVD)模拟分娩损伤,2次损伤后分别尿道旁注射干细胞(2×10^(6)个/只,注射体积为250μl)及等量生理盐水(250μl)。分别检测3组MVD术后立即、术后9 d、术后16 d的漏尿点压力(LPP)及最大膀胱容量(MBC)值的指标变化。提取大鼠尿道组织,部分制备石蜡切片并苏木素-伊红染色(HE染色)观察尿道组织病理变化,部分-80℃液氮保存行RNA提取及RNA测序。3组间比较采用独立样本t检验,组内比较采用单因素方差分析。结果干细胞注射组术后立即、术后9 d、术后16 d各时段LPP均高于生理盐水注射组[术后立即:(22.00±1.64)mmHg比(20.00±2.09)mmHg,t=22.900,P<0.05;术后9 d:(29.36±3.90)mmHg比(26.8±3.88)mmHg,t=15.030,P<0.01;术后16 d:(43.20±7.98)mmHg比(24.50±0.98)mmHg,t=6.558,P<0.05,1 mmHg=0.133 kPa]。干细胞注射组术后立即MBC与生理盐水组相似[(0.58±0.33)ml比(0.58±0.27)ml,t=3.733,P>0.05],术后9 d、术后16 d各时段MBC均高于生理盐水注射组[术后9 d:(0.77±0.14)ml比(0.74±0.19)ml,t=8.655,P<0.05、术后16 d:(0.83±0.34)ml比(0.53±0.09)ml,t=4.212,P<0.05]。干细胞注射组较对照组及生理盐水注射组组织学病理学有明显改变,主要表现为平滑肌数量较多、排列较规律,且部分存在新生肌纤维。RNA测序结果发现,干细胞注射组与对照组及生理盐水注射组中mRNA表达有显著差异,这些差异基因在肌肉收缩调节、血管生成、胶原纤维调节等多方面发挥作用。结论尿道旁注射hUC-MSCs可改善大鼠压力性尿失禁,可能与Wnt/腺苷酸活化蛋白激酶(AMPK)/丝�Objective To investigate the possible molecular mechanism of stress urinary incontinence(SUI)induced by simulated labor injury in rats treated by transurethral injection of human umbilical cord mesenchymal stem cells(hUC-MSCs).Methods Totally,12 specific pathogen free(SPF)-grade female Sprague-Dawley rats(6 weeks old,145-185 g)were selected and divided into stem cell injection group,saline injection group and blank control group by a random number table method,with 5,4 and 3 rats,respectively.Multiple vaginal balloon dilation(MVD)was used to simulate the birth injury in the stem cell injection group and the saline injection group.After the two injuries,stem cells(2×10^(6)/piece,250μl injection volume)and the equivalent amount of saline(250μl)were given paraurethral injection,respectively.The index changes of leakage point pressure(LPP)and maximum bladder volume(MBC)were detected immediately,9 d and 16 d after MVD in the three groups,respectively.Urethral tissue of rats was extracted,part of it was prepared by paraffin and stained with hematoxylin-eosin to observe the pathological changes of urethral tissue,and part of it was preserved in liquid nitrogen at-80℃for RNA extraction and RNA sequencing.Independent sample t test was used for comparison among the three groups,and one-way analysis of variance was used for comparison within the three groups.Results LPP in stem cell injection group was higher than that in normal saline injection group immediately,9 d and 16 d after surgery[Immediately after surgery:(22.00±1.64)mmHg vs.(20.00±2.09)mmHg,t=22.900,P<0.05;9 d after surgery:(29.36±3.90)mmHg vs.(26.8±3.88)mmHg,t=15.030,P<0.01;16 d after surgery:(43.20±7.98)mmHg vs.(24.50±0.98)mmHg,t=6.558,P<0.05,1 mmHg=0.133 kPa].The MBC of the stem cell injection group was similar to that of the normal saline group immediately after surgery[(0.58±0.33)ml vs.(0.58±0.27)ml,t=3.733,P>0.05],and that of the stem cell injection group was higher than that of the normal saline injection group at 9 d and 16 d after surgery[9

关 键 词：脐带干细胞 压力性尿失禁 RNA测序 细胞治疗 

分 类 号：R694.54[医药卫生—泌尿科学]