细胞因子CCL7通过受体CCR1增强干细胞归巢促进尿失禁恢复的研究

Study on CCR1-enhanced mesenchymal stem cells via CCL7 homing improving the functional recovery of stress urinary incontinence

目的:观察尿道局部注射细胞因子chemokine(C-C motif)ligand 7(CCL7)能否提高损伤后尿失禁模型中间充质干细胞(mesenchymal stem cells,MSC)归巢和CCR-1过表达的MSC归巢,探索CCL7对尿失禁的功能恢复。方法:尾静脉注射荧光转染MSC至尿失禁大鼠模型,1周后在4组[假尿失禁组(Sham SUI)、尿失禁合并MSC治疗组(SUI+MSC)、尿失禁合并CCR1增强表达MSC治疗组(SUI+MSC-CCR1)、尿失禁合并MSCCCR1加CCL7组(SUI+MSC-CCR1+CCL7)]中观察大鼠尿道组织中MSC归巢聚集情况。观察各组治疗后控尿恢复情况[假产伤假治疗组(sham injury+sham CCL7);产伤加假治疗组(injury+sham CCL7);产伤加治疗组(injury+CCL7)]。结果:SUI+MSC-CCR1+CCL7组在产伤后1天和1周后MSC局部归巢与存活情况显著增加(P<0.05),并显著高于sham SUI组、SUI+MSC组和SUI+MSC-CCR1组,且与对照组比较差异均有统计学意义(P<0.05)。1周后CCL7治疗后恢复情况明显优于尿失禁产伤后假治疗组,差异有统计学意义(P<0.05)。结论:CCL7与过表达CCR1可以促进MSC在损伤局部归巢与存活,CCL7对促进损伤后尿失禁模型的尿控水平恢复有显著意义。

Objective：To observe whether local urethral injection of cytokine chemokine（C-C motif）ligand 7（CCL7）can improve mesenchymal stem cells（MSC）homing and CCR-1-enhanced MSC homing to injured urethra,and to explore the recovery of the bladder function and the urinary continence after CCL7 injection with MSC homing on the simulated birth injury rat model for stress urinary incontinence（SUI）.Method：GFP fluorescence transfected MSC were isolated and cultured with tail vein intravenous injection on rat model of SUI.After one week of simulated brith injury and MSC and/or CCL7 delivery,MSC homing to local urethra with quantatitive analysis were compared between different four groups of sham SUI,SUI＋ MSC,SUI＋ MSC-CCR1 and SUI＋MSC-CCR1＋CCL7.Moreover,after one week of simulated brith injury and MSC and/or CCL7 delivery,the recovery of bladder function and urinary continence was also compared between three groups of sham injury＋sham CCL7 treatment（control）,injury＋sham CCL7 and injury＋CCL7.Result：SUI＋MSC-CCR1＋CCL7 group had significantly increased local urethal homing and survival of MSC after one day（P0.05）and one week（P0.05）injury,which were significant higher than those of groups of sham SUI,SUI＋ MSC and SUI＋MSC-CCR1（P0.05）one week after injury.One week after injury,whether CCL7 treatment or not,urinary continence level was significantly lower than that of sham injury.However,bladder function and urinary continence level have significant recovery one week after CCL7 treatment（P0.05）.Conclusion：CCL7 via CCR1 can promote the homing and survival of the MSC in local urethra,which may improve urinary incontinence recovery after simulated birth injury in rat model.