巨噬细胞移动抑制因子通过调控自噬抗H9c2心肌细胞缺氧/复氧损伤

doi:10.12092/j.issn.1009-2501.2018.05.008

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (5): 531-535.doi: 10.12092/j.issn.1009-2501.2018.05.008

巨噬细胞移动抑制因子通过调控自噬抗H9c2心肌细胞缺氧/复氧损伤

李金玉¹，黄丹梅²，张艳美²，石刚刚²，汪彬²

¹汕头大学医学院第二附属医院国家药物临床试验机构办公室，²药理学教研室，汕头 515041，广东

收稿日期:2017-10-20 修回日期:2017-12-30 出版日期:2018-05-26 发布日期:2018-05-16
通讯作者: 汪彬，男，博士，讲师，研究方向：心血管药理。 Tel：0754-88900432 E-mail：wangbin178.17@163.com
作者简介:李金玉，女，硕士，主管药师，研究方向：心血管药物研发，药物临床研究。 Tel：0754-88915796 E-mail：jinyuer8899@163.com
基金资助:
广东省自然科学基金联合资助基金项目（U0932005）；国家自然科学基金（81473215、81773729、81703508）

Macrophage migration inhibitory factor protects H9c2 cardiac myocytes against hypoxia/reoxygenation injury through regulation of autophagy

LI Jinyu¹, HUANG Danmei ², ZHANG Yanmei ², SHI Ganggang ², WANG Bin ²

¹Drug Clinical Trial Institution, the Second Affiliated Hospital,² Department of Pharmacology,Shantou University Medical College, Shantou 515041, Guangdong, China

Received:2017-10-20 Revised:2017-12-30 Online:2018-05-26 Published:2018-05-16

摘要/Abstract

摘要：

目的:研究巨噬细胞移动抑制因子（macrophage migration inhibitory factor,MIF）对H9c2心肌细胞缺氧/复氧（hypoxia/reoxygenation,H/R）过程中自噬的影响，并探讨其分子作用机制。方法:利用MIF特异性siRNA瞬时转染H9c2心肌细胞，建立H9c2心肌细胞H/R损伤模型，给予自噬经典抑制剂3-甲基嘌呤（3-MA），蛋白免疫印迹（Western blot）检测MIF、LC3、Cleaved caspase-3以及mTOR蛋白的表达。结果:干扰MIF后可抑制H/R诱导的心肌细胞自噬；自噬抑制剂3-MA抑制H/R诱导的心肌细胞自噬，减少细胞凋亡的发生；沉默MIF后可增加H/R过程中p-mTOR的表达。结论:MIF可通过抑制自噬减少H9c2心肌细胞H/R损伤，其作用机制可能与激活mTOR有关。

关键词: 巨噬细胞移动抑制因子, 缺氧/复氧, H9c2心肌细胞, 自噬, 凋亡

Abstract:

AIM: To investigate the effects of macrophage migration inhibitory factor (MIF) on autophagy of H9c2 cardiac myocytes during hypoxia/reoxygenation (H/R) injury so as to explore the molecular mechanism. METHODS: The MIF mRNA-targeting siRNA was transfected to H9c2 cardiac myocytes. The H/R models of H9c2 cardiac myocytes were established. The autophagy inhibitor 3-methyladenine (3-MA) was added.The levels of MIF, LC3, Cleaved caspase-3 and mTOR protein expression in H9c2 cardiac myocytes were detected by Western blot. RESULTS: MIF siRNA transfection inhibited H/R-induced autophagy. The inhibitor of autophagy 3-MA suppressed H/R-induced autophagy and decreased apoptosis. MIF knockdown increased the expression of p-mTOR during H/R. CONCLUSION: MIF inhibits autophagy in H9c2 cardiomyocytes subjected to H/R, which is related to active mTOR protein.

Key words: macrophage migration inhibitory factor, hypoxia/reoxygenation, H9c2 cardiac myocyte, autophagy, apoptosis

中图分类号:

R965.2

李金玉，黄丹梅，张艳美，石刚刚，汪彬. 巨噬细胞移动抑制因子通过调控自噬抗H9c2心肌细胞缺氧/复氧损伤[J]. 中国临床药理学与治疗学, 2018, 23(5): 531-535.

LI Jinyu, HUANG Danmei, ZHANG Yanmei, SHI Ganggang, WANG Bin. Macrophage migration inhibitory factor protects H9c2 cardiac myocytes against hypoxia/reoxygenation injury through regulation of autophagy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 531-535.

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巨噬细胞移动抑制因子通过调控自噬抗H9c2心肌细胞缺氧/复氧损伤

Macrophage migration inhibitory factor protects H9c2 cardiac myocytes against hypoxia/reoxygenation injury through regulation of autophagy

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