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在大鼠心肌梗死模型中,间充质干细胞通过神经生长因子增强心脏神经发芽。

Mesenchymal stem cells enhanced cardiac nerve sprouting via nerve growth factor in a rat model of myocardial infarction.

作者信息

Chen Jian, Zheng Shaoxin, Huang Hui, Huang Suihua, Zhou Changqing, Hou Jingying, Jiang Jieyu, Wang Jingfeng, Wu Wei, Wang Tong

机构信息

Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China. Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China.

出版信息

Curr Pharm Des. 2014;20(12):2023-9. doi: 10.2174/13816128113199990451.

DOI:10.2174/13816128113199990451
PMID:23844741
Abstract

BACKGROUND

Transplantation of mesenchymal stem cells (MSCs) alters the ventricular electrophysiologic properties after myocardial infarction (MI) in rats. However, it is unclear whether MSCs transplantation enhances the secretion of nerve growth factor (NGF) and affects cardiac sympathetic remodeling.

METHODS

MI was induced in 35 male Sprague-Dawley rats. Two weeks later, the animals were randomized to MSCs or phosphate buffer solution (PBS) injections into the infarcted myocardium. Six weeks thereafter, the expressions of NGF, growth associated protein 43 (GAP43) and tyrosine hydroxylase (TH) were measured and the density of GAP43 and TH positive nerves was calculated in the borderzone. NGF levels were detected in different culture conditions with neonatal rat ventricular myocytes (NRVMs, 2 × 10(5)/well) and MSCs (2 × 10(5)/well).

RESULTS

Compared with PBS, mRNA expression and protein levels of NGF, GAP43 and TH increased in the border zone after MSCs injection. Immunohistochemistry showed more GAP43- and TH-positive nerves in the MSCs than in the PBS group. Compared to monocultured MSCs, mono-cultured NRVMs secreted more NGF in vitro.

CONCLUSIONS

The expression of NGF increased after MSCs transplantation, which may affect sympathetic remodeling and the electrophysiological properties after MI. Paracrine factors secreted by MSC-CM may be involved in this process.

摘要

背景

间充质干细胞(MSCs)移植可改变大鼠心肌梗死后的心室电生理特性。然而,尚不清楚MSCs移植是否会增强神经生长因子(NGF)的分泌并影响心脏交感神经重塑。

方法

对35只雄性Sprague-Dawley大鼠诱导心肌梗死。两周后,将动物随机分为向梗死心肌注射MSCs或磷酸盐缓冲液(PBS)两组。六周后,检测梗死周边区NGF、生长相关蛋白43(GAP43)和酪氨酸羟化酶(TH)的表达,并计算GAP43和TH阳性神经的密度。在不同培养条件下,用新生大鼠心室肌细胞(NRVMs,2×10⁵/孔)和MSCs(2×10⁵/孔)检测NGF水平。

结果

与PBS组相比,注射MSCs后梗死周边区NGF、GAP43和TH的mRNA表达及蛋白水平均升高。免疫组织化学显示,MSCs组GAP43和TH阳性神经比PBS组更多。与单独培养的MSCs相比,单独培养的NRVMs在体外分泌更多的NGF。

结论

MSCs移植后NGF表达增加,这可能影响心肌梗死后的交感神经重塑和电生理特性。MSCs条件培养基分泌的旁分泌因子可能参与了这一过程。

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