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G-CSF促进Thy1.1+干细胞对球囊损伤后动脉的修复

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第5期
页码:
664-669
栏目:
基础研究
出版日期:
2010-06-22

文章信息/Info

Title:
Thy1.1+ stem cell transplantation and granulocyte colony-stimulating factor can repair injured arteries
作者:
刘华东董少红罗林杰姜昕
深圳市人民医院、暨南大学第二临床医学院心内科,广东 深圳 518020
Author(s):
LIU Hua-dong DONG Shao-hong LUO Lin-jie JIANG Xin
Department of Cardiology, Shenzhen People's Hospital, Shenzhen 518020, Guangdong, China
关键词:
粒细胞集落刺激因子Thy1.1干细胞血管再狭窄大鼠
Keywords:
granulocyte colony-stimulating factor bone marrow stem cells Thy1.1 antigen restenosis arterial injury rat
分类号:
R392.12
DOI:
-
文献标识码:
A
摘要:
目的: 探讨粒细胞集落刺激因子(G-CSF)动员自体干细胞及大鼠Thy1.1干细胞局部移植对大鼠颈总动脉球囊损伤后内膜增生的影响,评价干细胞移植对血管再狭窄的作用;探讨G-CSF与Thy1.1干细胞移植是否具有协同作用?G-CSF是否可以促进Thy1.1干细胞对动脉球囊损伤后的修复作用?方法: 将120只雌性大鼠随机分为4组(每组30只),即G-CSF组:于大鼠颈总动脉球囊损伤前7 d,开始皮下注射G-CSF 30 μg/(kg·d),连续注射7 d后进行球囊损伤;干细胞移植组:于颈总动脉球囊损伤后即刻,将约5×106 Thy1.1干细胞(来自4~6周SD大鼠)注入至损伤血管局部;联合移植组:按上述G-CSF组和干细胞移植物的要求,分别注射(入)G-CSF和Thy1.1干细胞;对照组:于颈总动脉球囊损伤后,局部注入等量的生理盐水。各组于术后即刻、3 d、7 d、14 d、28 d,取损伤血管段,HE染色后光镜下检查其病理变化,观察细胞的增殖。用原位杂交方法检查移植细胞的定植、分化情况;并通过RT-PCR方法分析内皮型一氧化氮合酶(eNOS)mRNA的表达。结果: G-CSF组及干细胞移植组内膜增生程度均低于对照组(P<0.05,P<0.01),eNOS mRNA表达明显高于对照组(P<0.05,P<0.01)。联合移植组内膜增生的程度低于其他组(P<0.05,P<0.01),eNOS mRNA的表达明显高于其他组(P<0.05,P<0.01)。结论: G-CSF动员自体干细胞及Thy1.1干细胞局部移植可促进大鼠颈总动脉球囊损伤后再内皮化的进程,抑制内膜增生过程,对球囊损伤具有修复作用,可预防血管成形术后的再狭窄。G-CSF与Thy1.1干细胞移植具有协同作用,G-CSF可促进Thy1.1干细胞对动脉球囊损伤后的修复作用。
Abstract:
AIM: To study the effects of granulocyte colony-stimulating factor (G-CSF) and Thy1.1 stem cell transplantation on endothelial hyperplasia, to evaluate the influence of stem cell transplantation on restenosis and to study whether G-CSF can cooperate with Thy1.1 stem cells to repair injured arteries. METHODS: One hundred twenty female Sprague Dawley (SD) rats were randomly divided into four groups (30/group): G-CSF group, stem cell transplantation group, combination transplantation group and control group. Rats in G-CSF group were injected daily with 30 μg G-CSF/kg for 7 days before carotid artery injury, rats in stem cell transplantation group were injected with 5×106 Thy1.1 stem cells (obtained from from 4- to 6-week-old male SD rats) into the injured artery after carotid artery injury, rats in combination transplantation group were injected with G-CSF and Thy1.1+ stem cells in the same manner as previously mentioned, and rats in control group were injected the same amount of saline into carotid artery. The animals were killed shortly after injury and 3, 7, 14, 21, and 28 days after balloon denudation and samples of carotid artery were harvested for pathological analysis and RT-PCR for eNOSmRNA. RESULTS: Intimal thickness was thinner in G-CSF group and stem cell transplantation group (P<0.05, P<0.01), eNOS mRNA expression was higher in G-CSF group and stem cell transplantation group compared with those in control group (P<0.05, P<0.01). Intimal thickness was lower and eNOSmRNA expression was higher in the combination transplantation group compared with those in other groups (P<0.05, P<0.01). CONCLUSION: G-CSF and stem cell transplantation accelerate reendothelialization and decrease neointimal formation following vascular injury, suggesting that stem cell transplantation may be a feasible strategy to prevent restenosis after PCI. G-CSF can cooperate with Thy1.1 stem cells to repair the injured artery.

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备注/Memo

备注/Memo:
收稿日期:2009-10-12.基金项目:深圳市科技局重点基金项目资助(200601011) 作者简介:刘华东,主治医师,博士Email:lhd2578@163.com
更新日期/Last Update: 2010-06-22