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过表达 miR-126 的间充质干细胞通过 AKT/ERK 相关通路增强缺血性血管生成。

Mesenchymal stem cells overexpressing MiR-126 enhance ischemic angiogenesis via the AKT/ERK-related pathway.

机构信息

Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.

出版信息

Cardiol J. 2011;18(6):675-81. doi: 10.5603/cj.2011.0032.

DOI:10.5603/cj.2011.0032
PMID:22113756
Abstract

BACKGROUND

This study was designed to examine whether transplantation of mesenchymal stem cells (MSCs) overexpressing miR-126 enhances angiogenesis in the infarcted myocardium of mice.

METHODS

MSCs were harvested from mice using density gradient centrifugation and adherent culture. MSCs were transfected with lentiviral vectors carrying mature miR-126. Mice models of myocardial infarction were established by ligation of coronary artery. The ligated animals were randomly divided into three groups (15 in each) and after two weeks, were intramyocardially injected at the heart infarct zone with miR-126-transfected MSCs (the miR-126-MSCs group), MSCs (the MSCs group), or medium (the PBS group). Six weeks later, histological study and echocardiographic assessment were performed.

RESULTS

Capillary density of the infarcted region was significantly improved in the miR-126- MSCs group compared to the MSC group and the PBS group (both p < 0.01). Western blot showed that ERK(1), pERK(1), AKT and pAKT gene were dramatically enhanced in the miR-126-MSC group compared to the MSC group and the PBS group (both p < 0.05). Echocardiography showed MiR-126 led to a sustained improvement in cardiac function for at least six weeks at the injected area, as assessed by left ventricular ejection fraction and fraction of shortening.

CONCLUSIONS

Transplantation of MSCs transfected with miR-126 can improve angiogenesis and cardiac function in the infarcted area of the hearts of mice, which may be due to stimulation of the AKT/ERK-related pathway.

摘要

背景

本研究旨在探讨过表达 miR-126 的间充质干细胞(MSCs)移植是否能增强小鼠梗死心肌的血管生成。

方法

采用密度梯度离心法和贴壁培养法从小鼠中分离 MSCs。用携带成熟 miR-126 的慢病毒载体转染 MSCs。结扎冠状动脉建立心肌梗死小鼠模型。结扎动物随机分为三组(每组 15 只),两周后在心梗区心肌内注射 miR-126 转染的 MSCs(miR-126-MSCs 组)、MSCs(MSCs 组)或培养基(PBS 组)。6 周后进行组织学研究和超声心动图评估。

结果

与 MSCs 组和 PBS 组相比,miR-126-MSCs 组梗死区的毛细血管密度明显提高(均 p<0.01)。Western blot 显示,与 MSCs 组和 PBS 组相比,miR-126-MSCs 组 ERK(1)、pERK(1)、AKT 和 pAKT 基因明显增强(均 p<0.05)。超声心动图显示,MiR-126 至少在注射区域持续改善心脏功能至少 6 周,左心室射血分数和缩短分数评估。

结论

转染 miR-126 的 MSCs 移植可改善小鼠梗死心肌的血管生成和心功能,这可能与 AKT/ERK 相关途径的激活有关。

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