慢病毒介导IGF—1基因修饰肌源性干细胞移植治疗雌性压力性尿失禁大鼠的实验研究
2018-09-26陈春经
陈春经
【摘要】 目的:探讨IGF-1基因修饰的肌源性干细胞(MDSCs)移植治疗雌性压力性尿失禁大鼠的作用及可能机制。方法:尿失禁大鼠随机分对照组即MDSCs移植组(n=15)和治疗组即IGF-1基因修饰的MDSCs移植组(n=15),以1×106个MDSCs/只注入尿道距膀胱约0.5 cm处,评价注射后尿道闭合功能情况、VEGF的表达情况及移植细胞存活情况。结果:与对照组比较,治疗组膀胱最大容量及腹压漏尿点压(ALPP)均升高,但差异无统计学意义(P>0.05);细胞存活数、VEGF蛋白表达量显著升高,差异有统计学意义(P<0.05)。结论:IGF-1基因修饰的MDSCs增强了其在移植环境中的生存能力,并通过其旁分泌功能,可能为治疗压力性尿失禁提供了一种新的方法。
【关键词】:胰岛素样生长因子-1; 肌源性干细胞; 压力性尿失禁; 生存能力
doi:10.14033/j.cnki.cfmr.2018.14.073 文献标识码 B 文章编号 1674-6805(2018)14-0-03
Therapeutic Efficacy of Lentiviral Vector Mediated IGF-1 Gene-Modified Muscle-Derived Stem Cells in Rats with Female Stress Urinary Incontinence/CHEN Chunjing.//Chinese and Foreign Medical Research,2018,16(14):170-172
【Abstract】 Objective:To explore that whether muscle-derived stem cells(MDSCs) pretreated with IGF-1 could promote urethral sphincter restoration in pudendal nerve-transected rat model.Method:Rats with Female Stress Urinary Incontinence were randomly divided into IGF-1/MDSCs injection group(the experimental group,n=15) and MDSCs injection group(the control group,n=15).MDSCs survival,urethral resistance function,western blot were carried out.Result:Compared with the control group,the maximum capacity of the bladder and abdominal leak point pressure(ALPP) were all increased(P>0.05),and the number of cells survival and expression of VEGF protein were increased significantly in the experimental group(P<0.05).Conclusion:MDSCs pretreated with IGF-1 that enhance their viability in the transplant environment and through their paracrine function may provide a new way to treat stress urinary incontinence.
【Key words】 IGF-1; Muscle-derived stem cell; Stress urinary incontinence; Viability
First-authors address:Sanming First Hospital Affiliated to Fujian Medical University,Sanming 365000,China
全球约有2亿多尿失禁患者,其中女性是男性的2~3倍,严重影响生活质量。且随着年龄的增长,发病率显著上升,其中压力性尿失禁(stress urinary incontinence,SUI)是最常见的类型[1]。其发病机制主要包括尿道高活动性和尿道固有括约肌功能障碍(intrinsic sphincter deficiency,ISD)[2]。老年女性SUI患者,几乎均合并存在ISD[3],现有的治疗方法尚不能完全解决伴有ISD的SUI患者的尿道括约肌闭合功能问题。因此,迫切需要从本质上寻求一种方法以改善尿道括约肌结构和功能缺陷。肌源性干细胞移植可以修复和改善骨骼肌功能[4-5],尿道横纹肌与骨骼肌同源,因此,肌源性干細胞移植也成为伴有ISD的SUI的一个研究热点。而随着年龄的增长,机体局部缺血缺氧、氧化应激等不利因素均可导致植入的干细胞存活率下降,进而影响细胞移植的治疗效果,因此,如何改善移植微环境、促进移植干细胞的存活,是首要解决的问题。研……
