膜微粒抑制缺氧无血清诱导的骨髓间充质干细胞的凋亡  

The role of microparticles in inhibiting hypoxia and serum deprivation induced apoptosis of bone marrow mesenchymal stem cells

作　　者：金培峰[1] 姜盛[1] 翁家侃[1,2] 王磊 丁露[3] 赵凯翔[1] 孙成超 JIN Peifeng;JIANG Sheng;WENG Jiakan;WANG Lei;Ding Lu;ZHAOKaixiang;SUN Chengchao(Department of Cardiothoracic Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China;Department of Cardiothoracic Surgery, Sir Run Run Shaw Hospital, Affiliated to Zhejiang University School of Medicine, Hangzhou 310000, China;Department of Ergology, Wenzhou Medical University, Wenzhou 325035, China)

机构地区：[1]温州医科大学附属第一医院心胸外科,浙江温州325015 [2]浙江大学医学院附属邵逸夫医院心胸外科,浙江杭州310000 [3]温州医科大学机能中心,浙江温州325035

出　　处：《温州医科大学学报》2019年第2期79-84,共6页Journal of Wenzhou Medical University

基　　金：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)

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0.5μg/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。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.

关 键 词：骨髓间充质干细胞 心肌梗死 膜微粒 凋亡 大鼠 

分 类 号：R654.2[医药卫生—外科学]