摘要
背景:血管损伤是球囊扩张术后常见的并发症,脐带间充质干细胞的发展为治疗血管损伤提供了新方法。目的:探讨转染白细胞介素8受体(IL-8RA/B)腺病毒的人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,hUCMSCs)修复损伤血管的机制。方法:培养原代人脐带间充质干细胞与脐静脉内皮细胞,转染含白细胞介素8重组腺病毒荧光载体。建立大鼠颈动脉损伤模型,将SD大鼠随机分为4组:IL-8RA/B-hUCMSCs组、IL-8RA/B-hUVECs组、Null-hUCMSCs组、对照组,手术后1,3,5 h分别从尾静脉输入0.5×106相应细胞(500μL),对照组输注同等剂量的生理盐水,30 min后取颈动脉血管,观测绿色荧光蛋白的表达;24 h后采用ELISA测定血清中炎性因子和抗炎因子水平;24 h后采用免疫组化观察中性粒细胞和单核/巨噬细胞的浸润;14 d后伊文思蓝染色观察血管再内皮化及纤维化;28 d后采用苏木精-伊红染色观察血管新内膜增生。结果与结论:①移植细胞后30 min,观察到损伤血管内膜有绿色荧光蛋白的表达,IL-8RA/B-hUCMSCs组荧光表达量高于其他3组;②移植细胞后24 h,IL-8RA/B-hUCMSCs组血清中炎性因子水平明显低于其他3组,而抗炎因子白细胞介素10水平高于其他3组(P <0.05),并且IL-8RA/B-hUCMSCs组炎性细胞浸润明显减少;③移植细胞后14 d,过表达白细胞介素8受体的hUCMSCs促进损伤血管再内皮化,减少血管纤维化;④移植细胞后28 d,IL-8RA/B-hUCMSCs明显减少损伤血管新内膜增生;⑤结果表明,白细胞介素8受体提高hUCMSCs的靶向归巢能力,使hUCMSCs能定向迁移至血管损伤部位,抑制炎症,促进血管再内皮化,减少新内膜增生,促进血管修复。
BACKGROUND:Vascular injury is a common complication after balloon dilatation.The development of umbilical cord mesenchymal stem cells(UC-MSCs)provides a new method for treating vascular injury.OBJECTIVE:To investigate the mechanism underlying the repair of damaged blood vessels by human UC-MSCs(hUC-MSCs)transfected with interleukin-8RA/B(IL-8RA/B)adenovirus.METHODS:hUC-MSCs and human umbilical vein endothelial cells(hUVECs)were collected and transfected with adenovirus vectors containing human IL-8RA and/or IL-8RB cDNAs and green fluorescent protein.A rat model of carotid artery injury was established.Sprague-Dawley rats were randomly divided into four groups:IL-8RA/B-hUCMSCs group,Il-8ra/B-hUVECs group,Null-hUCMSCs group,and control group,followed by injection of 0.5×106 corresponding cells(500μL)and same volume of normal saline via the tail vein respectively at 1,3,and 5 hours post-surgery.After 30 minutes of injection,the carotid artery was taken and the expression of green fluorescent protein was observed.After 24 hours,the serum levels of inflammatory and anti-inflammatory factors were measured by ELISA;and the infiltration of neutrophil cells and mononuclear macrophages was observed by immunohistochemistry.After 14 days,Evans blue staining was used to observe vascular endothelialization and fibrosis.After 28 days,the neointimal hyperplasia was observed by hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)After 30 minutes of IL-8RA/B-hUC-MSCs infusion,the expression of green fluorescent protein was observed in the injured vascular intima,and the fluorescence expression was higher than that of the other three groups.(2)After 24 hours of IL-8RA/B-hUC-MSCs infusion,the expression of inflammatory factors in the serum was significantly lower than that of the other three groups,while the expression of anti-inflammatory factor interleukin-10 was higher than that of the other three groups(P<0.05).In addition,inflammatory cell infiltration in the IL-8RA/B-hUC-MSCs group decreased significantly.(3)hUC-MSCs overex
作者
朱兵兵
何海斌
邓江华
王文强
慕晓玲
Zhu Bingbing;He Haibin;Deng Jianghua;Wang Wenqiang;Mu Xiaoling(School of Medicine,Shihezi University,Shihezi 832000,Xinjiang Uygur Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2021年第1期61-66,共6页
Chinese Journal of Tissue Engineering Research
基金
新疆兵团社会发展科技攻关与成果转化计划(2016AD013),项目负责人:慕晓玲
自治区研究生教育创新计划科研创新项目(XJGRI201604),项目负责人:慕晓玲。
关键词
人脐带间充质干细胞
白细胞介素8受体
血管损伤
炎性因子
血管内皮
human umbilical cord mesenchymal stem cells
interleukin-8RA/B
vascular injury
inflammatory factor
vascular endothelium
