【摘要】 目的观察人脐带间充质干细胞(hUCMSCs)对NOD小鼠皮肤组织AGEs/RAGE/NF-κB信号通路的影响,探讨其对于改善糖尿病皮肤组织"隐性损害"的机制。方法 NOD小鼠43只,饲养9周后分为正常对照组(NC组,饲养9周后未发病的NOD小鼠,n=12)和模型组(DM组,饲养后糖尿病发病的NOD小鼠,n=31);DM组再分为干细胞组(MSC,n=11)、胰岛素组(INS,n=10)及空白对照组(BC,n=10)。各组予相应干预,8周后检测随机血糖,并取皮肤组织,光镜下观察结构;ELISA检测AGEs水平;RT-qPCR检测RAGE、NF-κB p65、白介素6(IL-6)、TNF-αmRNA表达水平。结果镜下观察,BC组皮肤组织出现结构紊乱,厚度变薄,细胞肿胀,胶原稀疏等病理改变,MSC组对比前者则有明显改善。与BC组比较,其余3组随机血糖、皮肤AGEs水平及上述4种因子mRNA的表达水平均降低(P<0. 05);与MSC组比较,INS组均增高(P<0. 05)。结论 h UCMSCs可一定程度上抑制AGEs/RAGE/NF-κB信号通路,该作用可能是改善糖尿病皮肤组织"隐性损害"的机制之一。更多还原

【Abstract】 ObjectiveTo observe the effects of human umbilical cord mesenchymal stem cells(h UCMSCs)on AGEs/RAGE/NF-κB signaling pathway in NOD mice skin tissue,and to explore its effect on improving the"hidden damage"of diabetic skin tissue. mechanism.MethodsA total of 43 NOD mice were divided into normal control group(NC,n=12)and diabetic model group(DM,n=31)after 9 weeks of feeding. The model group was further divided into stem cell treatment group(MSC,n=11),insulin treatment group(INS,n=10)and blank control group(BC,n=10). Random blood glucose(Glu)was measured after 8 weeks of intervention. The biopsy skin tissue was observed under a light microscope. The concentration of AGEs was detected by ELISA. The mRNA expression levels of RAGE,NF-κB p65,IL-6 and TNF-α were detected by RT-qPCR.ResultsUnder the microscope,the skin tissue of the BC group showed structural disorder,thinner thickness,swollen cells,sparse collagen and other obvious pathological changes. The MSC group showed significant improvement compared with the former. Compared with BC group,the levels of Glu,skin AGEs and mRNA expression of the above four factors were decreased in the other three groups(P<0. 05). Compared with MSC group,the above indicators of INS group increased(P<0. 05).ConclusionhUCMSCs can inhibit AGEs/RAGE/NF-κB signaling pathway to a certain ex-tent,which may be one of the mechanisms to improve the"hidden damage"of diabetic skin tissue.更多还原