hucMSCs-Exo对子痫前期孕鼠血清sFLt-1 VEGF的影响

摘要

Objective To investigate whether human umbilical cord mesenchymal stem cell-derived exosomes(hucMSCs-Exo)have a repairing effect on the preeclampsia vascular endothelium and possible mechanisms. Methods Exosomes were successfully isolated and identified from human umbilical cord mesenchymal stem cells(hucMSCs)by ultracentrifugation. Fifty consecutive SD rats were successfully injected with L-NAME intraperitoneally to establish preeclampsia model rats. The model rats were divided into 5 groups:PE group(n=10);PE+NC group(n=10);L-Exo group(n=10),M-Exo group(n=10),H-Exo group(n=10). Six days after treatment,rats were sacrificed to take blood and placental tissue. Immunohistochemistry was used to detect the concentration of microvessels in the placenta. Elisa was used to detect the serum concentrations of sFLt-1 and VEGF in each group. Results Firstly,the primary hucMSCs-Exo was successfully isolated and identified;hUCMSCs-Exo increased the microvessel density of the placenta. Compared with the PE and NC groups,the MVD was significantly increased in the L-Exo,M-Exo and H-Exo groups. H-Exo was higher than L-Exo group and M-Exo group(P0.05). The results of serum sFLt-1 and VEGF Elisa also suggested that hucMSCs-Exo could repair vascular endothelial function,and with the increase of exosome concentration,the vascular endothelial repair function was stronger,which was in a dose-dependent manner. Conclusion hUCMSCs-Ex can effectively promote the repair of vascular endothelial function and provide a new treatment direction for clinical treatment of preeclampsia. The mechanism needs to be further studied.%目的 探讨人脐带间充质干细胞来源的外泌体(hucMSCs-Exo)对子痫前期血管内皮是否具有修复作用及可能的作用机制.方法 利用超离心方法从人脐带间充质干细胞(hucMSCs)中成功分离出外泌体,并进行鉴定;取50只受孕成功的SD大鼠连续腹腔注射L-NAME,建立子痫前期模型大鼠,将模型大鼠分为5组,分别为PE组(n=10)、PE+NC组(n=10)、L-Exo组(n=10)、M-Exo组(n=10)、H-Exo组(n=10).治疗后6d,处死大鼠取血及胎盘组织.采用免疫组化法检测胎盘组织中微血管浓度,Elisa检测各组大鼠血清中sFLt-1、VEGF浓度.结果 首先成功分离提取原代hucMSCs-Exo并进行鉴定;hucMSCs-Exo能够增加胎盘微血管密度,PE组和PE+NC组比较,微血管密度(MVD)在L-Exo组、M-Exo组和H-Exo组明显升高,H-Exo高于L-Exo组和M-Exo组(P0.05).血清sFLt-1和VEGF Elisa结果同样提示hucMSCs-Exo可修复血管内皮功能,其血管内皮修复功能随外泌体作用浓度的增加而增强,呈现出剂量依赖性.结论 hucMSCs-Ex能有效促进血管内皮功能的修复,为临床治疗子痫前期提供新的治疗方向,其机制有待进行更深入的研究.