中国组织工程研究

中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (30): 4852-4856.doi: 10.12307/2022.737

• 干细胞基础实验 basic experiments of stem cells • 上一篇    下一篇

丹参酮ⅡA对缺氧条件下心肌前体细胞存活和归巢能力影响的机制

赵  琳，樊晨星，李  昆   

  1. 锦州医科大学附属第一医院检验科，辽宁省锦州市   121000
  • 收稿日期:2021-09-26 接受日期:2021-10-30 出版日期:2022-10-28 发布日期:2022-03-29
  • 通讯作者: 李昆，主任检验师，硕士生导师，锦州医科大学附属第一医院检验科，辽宁省锦州市 121000
  • 作者简介:赵琳，女，1996年生，满族，锦州医科大学在读硕士，主要从事中药药理学方面的研究。
  • 基金资助:
    辽宁省教育厅科学技术研究项目(JYTQN2020024)，项目负责人：李昆

Mechanism underlying tanshinone IIA effect on survival and homing ability of myocardial precursor cells under hypoxia

Zhao Lin, Fan Chenxing, Li Kun   

  1. Department of Clinical Laboratory, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, Liaoning Province, China
  • Received:2021-09-26 Accepted:2021-10-30 Online:2022-10-28 Published:2022-03-29
  • Contact: Li Kun, Chief laboratorian, Master’s supervisor, Department of Clinical Laboratory, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, Liaoning Province, China
  • About author:Zhao Lin, Master candidate, Department of Clinical Laboratory, First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, Liaoning Province, China
  • Supported by:
    the Science and Technology Research Project of the Education Department of Liaoning Province, No. JYTQN2020024 (to LK)

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摘要：

文题释义：
H9c2细胞：来源于胚胎期BD1X大鼠的心脏组织，可以分化为心肌细胞，该细胞株易培养，而且差异性小，常被用作研究心肌分化的前体干细胞模型。
ERK1/2信号通路：激活的ERK1/2可在胞质中调控靶蛋白，也可转运入胞核并在核内磷酸化多种调控基因表达的转录因子，参与细胞存活与迁移调控。

背景：干细胞移植治疗缺血性心脏病尚存在诸多需要解决或完善的问题，其中移植细胞能够归巢到心肌受损处并存活下来是干细胞治疗缺血性心脏病的关键。
目的：评估丹参酮ⅡA干预对缺氧条件下心肌前体细胞存活和归巢能力的影响并探讨其相关机制。
方法：选用H9c2细胞作为心肌前体细胞模型，分别以氯化钴、丹参酮ⅡA+氯化钴、丹参酮ⅡA+氯化钴+AG126(ERK1/2通路抑制剂)处理H9c2细胞，MTS法检测细胞增殖情况、流式细胞法分析细胞凋亡率、划痕法评估细胞向损伤区域迁移情况、Western blot法检测ERK1/2通路相关蛋白(ERK1/2、p-ERK1/2、HIF-1α、cleaved caspase-3、MMP-9)的表达。
结果与结论：①与氯化钴组比较，丹参酮ⅡA+氯化钴处理的H9c2细胞增殖加快、凋亡减少、向损伤区迁移能力增强，且在此过程中，ERK1/2表达无明显变化(P > 0.05)，p-ERK1/2、HIF-1α、MMP-9表达明显增多(P < 0.05)，cleaved caspase-3表达明显减少(P < 0.05)；②与丹参酮ⅡA+氯化钴组比较，丹参酮ⅡA+氯化钴+ AG126处理组H9c2细胞中ERK1/2通路明显被抑制，且细胞存活能力以及向损伤区迁移能力均明显降低；③结果表明，丹参酮ⅡA能通过调控ERK1/2通路促进缺氧条件下心肌前体细胞的存活和归巢。

https://orcid.org/0000-0003-3570-0667 (赵琳) 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 缺血性心脏病, 心肌再生, 丹参酮ⅡA, 缺氧, 心肌前体细胞, 存活, 归巢, ERK1/2通路

Abstract: BACKGROUND: There are still many problems to be solved or perfected in the treatment of ischemic heart disease by stem cell transplantation. Among them, the key of stem cell transplantation in the treatment of ischemic heart disease is that the transplanted cells can home to the damaged myocardium and survive there.  
OBJECTIVE: To evaluate the effect of tanshinone IIA on the survival and homing ability of myocardial precursor cells under hypoxia and investigate its related mechanism.
METHODS:  H9c2 cells were selected as the myocardial precursor cell model. The H9c2 cells were respectively intervened with cobalt chloride, tanshinone IIA+cobalt chloride and tanshinone IIA+cobalt chloride+AG126(ERK1/2 pathway inhibitor). Cell proliferation was detected with MTS method. Cell apoptosis was analyzed using flow cytometry. Cell migration was evaluated by scratch assay. The expression levels of ERK1/2 pathway related proteins (ERK1/2, p-ERK1/2, HIF-1α, cleaved caspase-3, and MMP-9) were assessed using western blot assay.  
RESULTS AND CONCLUSION: (1) Compared with the cobalt chloride group, the proliferation of H9c2 cells treated with cobalt chloride combined with tanshinone IIA was accelerated; the apoptosis was reduced; and the homing ability was enhanced. During this process, the expression of ERK1/2 had no significant changes (P > 0.05), but the expression levels of p-ERK1/2, HIF-1α, and MMP-9 were significantly increased (P < 0.05), and the expression of cleaved caspase-3 was significantly decreased (P < 0.05). (2) Compared with the cobalt chloride + tanshinone IIA group, the ERK1/2 pathway in H9c2 cells treated with cobalt chloride + tanshinone IIA + AG126 was significantly inhibited, and the ability of cell survival and migration to the injured area was significantly decreased. (3) The results showed that tanshinone IIA could promote the survival and homing ability of myocardial precursor cells under hypoxia by regulating ERK1/2 pathway.

Key words: ischemic heart disease, myocardial regeneration, tanshinone IIA, hypoxia, myocardial precursor cells, survival, homing, ERK1/2 pathway

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