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2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷在体外诱导大鼠心脏干细胞增殖。

Proliferation of rat cardiac stem cells is induced by 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside in vitro.

作者信息

Song Fan, Zhao Jing, Hua Fei, Nian Lun, Zhou Xuan-Xuan, Yang Qian, Xie Yan-Hua, Tang Hai-Feng, Sun Ji-Yuan, Wang Si-Wang

机构信息

Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.

Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.

出版信息

Life Sci. 2015 Jul 1;132:68-76. doi: 10.1016/j.lfs.2015.04.001. Epub 2015 Apr 25.

DOI:10.1016/j.lfs.2015.04.001
PMID:25916801
Abstract

AIM

To study the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG) on proliferation of rat cardiac stem cells (CSCs) in vitro.

MATERIALS AND METHODS

C-kit(+) cells were isolated from neonatal (1 day old) Sprague-Dawley rats by using flow cytometry. Optimal THSG treatment times and doses for growth of CSCs were analyzed. CSCs were treated with various THSG doses (0, 1, 10, and 100 μM) for 12h.

RESULTS

Sorted c-kit(+) cells exhibited self-renewing and clonogenic capabilities. Cell Counting Kit (CCK-8) and Proliferating Cell Nuclear Antigen (PCNA) ELISA test positive cells were significantly increased in THSG-treated groups compared with untreated controls. The percentage of S-phase cells also increased after THSG treatment. Moreover, we show that some c-kit(+) cells spontaneously express vascular endothelial growth factor (VEGF), T-box transcription factor (Tbx5), hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2), hyperpolarization-activated cyclic nucleotide gated 4 (HCN4), alpha myosin heavy chain (αMHC), and beta myosin heavy chain (βMHC) mRNA, and stem cell antigen 1 (Sca-1), cardiac troponin-I, GATA-4, Nkx2.5, and connexin 43 protein were also assessed in CSCs. However, their expression was significantly increased with THSG treatment when compared to untreated controls.

CONCLUSION

THSG can increase proliferation of rat CSCs in vitro and thus, shows promise as a potential treatment strategy for stimulating endogenous stem cells to help repair the injured heart after myocardial infarction in patients.

摘要

目的

研究2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(THSG)对大鼠心脏干细胞(CSCs)体外增殖的影响。

材料与方法

采用流式细胞术从新生(1日龄)Sprague-Dawley大鼠中分离C-kit(+)细胞。分析CSCs生长的最佳THSG处理时间和剂量。将CSCs用不同剂量(0、1、10和100μM)的THSG处理12小时。

结果

分选的C-kit(+)细胞表现出自我更新和克隆形成能力。与未处理的对照组相比,噻唑蓝(CCK-8)和增殖细胞核抗原(PCNA)ELISA检测阳性细胞在THSG处理组中显著增加。THSG处理后S期细胞百分比也增加。此外,我们发现一些C-kit(+)细胞自发表达血管内皮生长因子(VEGF)、T盒转录因子(Tbx5)、超极化激活环核苷酸门控通道2(HCN2)、超极化激活环核苷酸门控通道4(HCN4)、α肌球蛋白重链(αMHC)和β肌球蛋白重链(βMHC)mRNA,并且还在CSCs中评估了干细胞抗原1(Sca-1)、心肌肌钙蛋白I、GATA-4、Nkx2.5和连接蛋白43蛋白。然而,与未处理的对照组相比,THSG处理后它们的表达显著增加。

结论

THSG可增加大鼠CSCs的体外增殖,因此,作为一种潜在的治疗策略,有望刺激内源性干细胞帮助修复心肌梗死后患者受损的心脏。

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