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|本期目录/Table of Contents|

二十碳五烯酸抑制棕榈酸诱导的乳鼠心肌细胞凋亡及机制

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第3期
页码:
254-259
栏目:
基础研究
出版日期:
2018-03-25

文章信息/Info

Title:
Eicosapentaenoic acid inhibits palimitate-induced apoptosis of neonatal mouse cardiomyocytes and underlying mechanisms
作者:
康 黎1; 邹 勇2; 李宏增1; 刘 军1; 张 莹1
(1.第四军医大学唐都医院老年病科，陕西 西安 710038；2.长庆油田职工医院心血管内科，陕西 西安 710201)
Author(s):
KANG li1;  ZOU Yong2;  LI Hong-zeng1;  LIU Jun1;  ZHANG Ying1
(1.Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, China, 2.Department of Cardiology, Hospital of Changqing Oilfield, Xi’an 710201, Shaanxi, China)
关键词:
二十碳五烯酸; 棕榈酸; 心肌细胞; 凋亡
Keywords:
EPA;  PAL;  Myocardial cell;  apoptosis
分类号:
R915
DOI:
-
文献标识码:
A
摘要:
目的 探讨二十碳五烯酸(Eicosapentaenoic Acid，EPA)对棕榈酸（palimitate，PAL）诱导的乳鼠心肌细胞凋亡的影响及其机制。方法 以PAL诱导的乳鼠心肌细胞为模型，分为对照组、PAL组、EPA+PAL组、EPA+PAL+Compound C组；采用MTT法检测细胞存活率，TUNEL化学染色检测细胞凋亡率，Western blot检测乳鼠心肌细胞cleaved caspase 3、动力相关蛋白(Dynamin-related protein,Drp)1表达水平和腺苷酸活化蛋白激酶（AMP-activated protein kinase,AMPK）的磷酸化水平。结果 不同浓度PAL刺激细胞24 h，与对照组相比，400 μmol/L PAL诱导后细胞活性显著降低，凋亡率明显增加（P<0.05），凋亡相关蛋白cleaved caspase-3活性上调(P<0.05)，同时AMPK磷酸化水平降低(P<0.05)，Drp1表达增加(P<0.05)。但50 μmol/L EPA处理却通过激活AMPK磷酸化，抑制Drp1的表达，进而逆转PAL诱导的细胞凋亡（P<0.05）。AMPK阻断剂Compound C则通过抑制AMPK，激活Drp1活性，增加凋亡相关蛋白cleaved caspase 3的活性，从而削弱了EPA抵抗PAL诱导的细胞凋亡（P<0.05）。结论 EPA可通过激活AMPK，减少Drp1表达水平，从而抑制PAL诱导的乳鼠心肌细胞凋亡，这些结果为深入认识EPA的心肌保护作用提供了新的实验依据。
Abstract:
AIM To investigate the effect and the molecular mechanisms of EPA on apoptosis in palimitate-induced myocardial cells. METHODSA palmitate-induced mouse myocardial cell model was utilized. Groups were randomly divided into a blank control group, a PAL-stimulated group, an EPA+PAL stimulated group, and an EPA+PAL+Compound C group. Cell viability ratio was determined by MTT and apoptosis was assessed by TUNEL assay. Western blot method was utilized to detect the expression of cleaved caspase 3, Drp1 and p-AMPK. RESULTSWhen myocytes were exposed to palmitate (400μmol/L) for 24 h, the myocytes showed decrease of cell viability (P<0.05), increase in number of TUNEL-positive cells (P<0.05), and activation of cleaved caspase 3, as compared with control (P<0.05). Additionally, PAL-induced apoptosis decreased phosphorylation of AMPK (P<0.05) and up-regulated the protein level of Drp1 (P<0.05). Further, co-incubation of the cell with EPA (50 μmol/L) and PAL suppressed PAL-induced apoptosis by activated phosphorylation of AMPK and inhibited expression of Drp1 (P<0.05). Compound C, an AMPK antagonist, attenuated the protective effects of EPA against PAL-induced apoptosis though suppression of AMPK phosphorylation (P<0.05) which subsequently activated expression of Drp1 and cleaved caspase 3 (P<0.05). CONCLUSIONEPA inhibits PAL-induced apoptosis in neonatal mouse cardiomyoctes via activation of the AMPK pathway and suppression of Drp1 expression. These results provide new insights for myocardial protective effects of EPA.

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备注/Memo

备注/Memo:
收稿日期：2017-03-31.基金项目：2016年保健专项科研项目资助（16BJZ39） 通讯作者：李宏增，副主任医师，主要从事老年病学研究 Email:Lli hong zeng@163.com 作者简介：康黎，主治医师 Email:klgcckl@163.com
更新日期/Last Update: 1900-01-01