脂肪间充质干细胞来源外泌体对缺氧/复氧诱导的心肌细胞凋亡的影响

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Abstract Objective To investigate the effect of mouse adipose-derived mesenchymal stem cells (mASCs) derived exosomes (Exo) on hypoxia/reoxygenation (H/R) induced apopotosis of cardiomyocytes neonatal mouse cardiomyocytes. Methods The mascs-derived Exo (mascs-exo) was isolated and extracted by ultra-high speed centrifugation. The Exo was observed and identified by transmission electron microscopy (TEM), nanoparticle tracer analysis (NTA) and Western blot (WB). C57BL/6 suckled rat cardiomyocytes were extracted by differential adherent method. Expression of CTnI and conexin43 was detected by immunofluorescence. Pkh-26 was labeled Exo to indicate the uptake capacity of cardiomyocytes. The experiment was divided into three groups: normal control group (control group), hypoxia/reoxygenation group (H/R group) and hypoxia/reoxygenation + mascs-exo group (H/R+ mascs-exo group). Apoptosis of was detected by TUNEL staining. The expression level of apoptosis-related protein was detected by WB. Results compared with the control group, the apoptosis rate of cardiomyocytes in the H/R group was increased (P ＜ 0.01), and the apoptosis rate of cardiomyocytes in the H/R+ mascs-exo group was decreased (P ＜ 0.05). Compared with the control group, p-PI3K /PI3K, p-Akt /Akt, and Bcl-2 /Bax were decreased in the H/R group (P ＜ 0.01), while the cleaved caspase-9/caspase-9 ratio was increased (P ＜ 0.01). Compared with H/R group, the ratio of p-PI3K/PI3K, p-Akt /Akt and Bcl-2 /Bax in H/R+ mascs-exo group was increased (P ＜ 0.05 or P ＜ 0.01), and the ratio of cleaved caspase-9/caspase-9 was decreased (P ＜ 0.01). Conclusion mASCs-Exo can inhibit H/R induction of cardiomyocytes apoptosis, which may be mediated by activation of the PI3K/Akt signaling pathway.

Key words： Adipose-derived mesenchymal stem cells Exosomes Primary cardiomyocytes Hypoxia/reoxygenation PI3K/Akt signaling pathway

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	LIANG Zheng ZHONG Jianfeng WU Yancong WEN Wen CHEN Can LI Bo

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LIANG Zheng ZHONG Jianfeng WU Yancong WEN Wen CHEN Can LI Bo. Effect of the exosomes extracted from adipose-derived mesenchymal stem cells on hypoxia/reoxygenation-induced cardiomyocyte apoptosis[J]. 中国医药导报, 2020, 17(5): 4-7,22.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2020/V17/I5/4

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