膜微粒抑制缺氧无血清诱导的骨髓间充质干细胞的凋亡

doi:10.3969/j.issn.2095-9400.2019.02.001

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摘要目的：明确心肌梗死后血液来源的膜微粒（MPs）抑制缺氧无血清诱导的骨髓间充质干细胞（BMSCs）凋亡的作用并探讨其相关机制。方法：利用结扎SD大鼠左冠脉前降支的方法来制作急性心肌梗死模型，然后提取血液中的MPs。提取培养SD大鼠的BMSCs，并建立缺氧无血清的干细胞凋亡模型。分别按照不同浓度（即0.5 μg/mL、1 μg/mL和2 μg/mL）的MPs对干细胞进行预处理，分别利用Hoechst染色、Tunel检测、AnnexinV/PI流式细胞学、Western blot检测caspase-3来揭示MPs抑制BMSCs的凋亡作用，并用Akt信号通路的通路抑制剂AZD5363来初步探讨其抗凋亡的相关机制。结果：大鼠心肌梗死后血液来源的MPs能够有效抑制缺氧无血清诱导的BMSCs的凋亡（P＜0.01）；并且其抗凋亡作用呈现出浓度依赖性，0.5 μg/mL 浓度的MPs亦能达到显著抗凋亡作用（P＜0.05）。其机制主要是通过激活Akt信号通路来实现。结论：心肌梗死后血液来源的MPs能有效抑制缺氧无血清诱导的BMSCs的凋亡。

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	金培峰
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	赵凯翔
	孙成超

关键词 ：骨髓间充质干细胞, 心肌梗死, 膜微粒, 凋亡, 大鼠

Abstract：Objective: To investigate the effects of myocardial infarction plasma-derived microparticles (MPs) on the hypoxia and serum deprivation induced apoptosis of bone marrow mesenchymal stem cells (BMSCs). Methods: Myocardial infarction (MI) was created by left anterior descending artery ligation in Lewis rats. The plasma-derived MPs were isolated 24 hours later from the blood. In order to study the protective effects of MPs on BMSCs under the conditions of hypoxia and serum deprivation (hypoxia/SD). BMSCs were pretreated with different concentrations (0.5 μg/mL, 1 μg/mL, and 2 μg/mL) of MPs before the apoptosis was induced. Cell apoptosis was evaluated by using flow cytometry of Annexin V/PI staining, Hoechst staining and the Tunel assay. Expression of cleavage of caspase-3 were assessed by Western blotting. The Akt pathway inhibitor AZD5363 was used to reveal the mechanism of MPs inhibiting BMSCs apoptosis. Results: The MPs derived from the myocardial infarction rats could remarkably prevent BMSCs from Hypoxia/SD induced apoptosis through activating Akt signaling pathway, and its anti-apoptosis effect showed a concentration dependence (0.5-2 μg/mL) (P<0.01). Conclusion: MPs derived from myocardial infarction could effectively inhibit hypoxia/SD induced apoptosis of BMSCs.

Key words： mesenchymal stem cells myocardial infarction microparticles apoptosis rats

基金资助:国家自然科学基金青年基金资助项目（81500220）；温州市科技计划项目（Y20150072）。

作者简介: 金培峰（1984-），男，浙江乐清人，主治医师，硕士。

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https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2019.02.001 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I2/79

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