环氧二十碳三烯酸抑制剂通过AKT/FoxO1信号通路抑制棕榈酸诱导的心肌细胞凋亡  

14,15-EET inhibited palmitate induced H9c2 cells apoptosis through AKT/FoxO1 signaling pathways

作　　者：张洁[1] 张涛[2] 廖宇峰[3] 王扬淦[1] 万静[1] Zhang Jie;Zhang Tao;Liao Yufeng;Wang Yanggan;Wan Jing(Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430000;School of Information Science and Engineering, Wuhan University of Science and Technology, Wuhan 430000;Department of Cardiology, Guoyao Dongfeng General Hospital, Hubei University of Medicine, Shiyan 442000, China)

机构地区：[1]武汉大学中南医院心内科,武汉430000 [2]湖北医药学院附属国药东风总医院心内科,十堰442000 [3]武汉科技大学信息科学与工程学院,武汉430065

出　　处：《中国组织化学与细胞化学杂志》2018年第1期13-17,共5页Chinese Journal of Histochemistry and Cytochemistry

摘　　要：目的观察14,15-环氧二十碳三烯酸(14,15-epoxyeicosatrienoic acid,14,15-EET)及其抑制剂14,15-环氧二十碳-5(Z)-烯酸(14,15-epoxyeicosa-5(Z)-enoic acid,14,15-EEZE)对棕榈酸(palmitate acid,PA)诱导心肌细胞凋亡的作用及机制。方法 14,15-EET和14,15-EEZE单独或联合作用于PA诱导后的H9c2细胞,采用噻唑蓝比色法检测细胞增殖,流式细胞术检测细胞凋亡,免疫印迹法测定细胞p-AKT和p-Fox O1蛋白表达水平。结果流式细胞术检测显示,PA诱导下H9c2细胞凋亡率上升,14,15-EET的作用可降低细胞凋亡率,而加用14,15-EEZE使细胞凋亡率上升,14,15-EEZE的单独作用也可提高PA诱导下H9c2细胞的凋亡率。免疫印迹分析显示,PA可降低H9c2细胞p-AKT和p-Fox O1蛋白表达水平,14,15-EET的作用可使p-AKT和p-Fox O1蛋白表达水平明显上升,而加用14,15-EEZE后p-AKT和p-Fox O1的蛋白表达水平明显下降,14,15-EEZE的单独作用可使PA诱导下H9c2细胞的p-AKT和p-Fox O1的表达水平明显下降。结论 14,15-EET可能通过促进AKT/Fox O1信号通路活性抑制棕榈酸诱导的H9c2细胞凋亡,而其抑制剂14,15-EEZE可能通过抑制AKT/Fox O1信号通路活性抑制14,15-EET的抗棕榈酸诱导H9c2心肌细胞凋亡的作用。Objective To investigate the effects of14,15-epoxyeicosatrienoic acid(14,15-EET)and its inhibitor,14,15-epoxyeicosa-5(Z)-enoic acid(14,15-EEZE)on H9c2cell apoptosis induced by palmitic acid(PA).The possible mechanisms were also explored.Methods H9c2cells were pre-incubated with PA before treated by14,15-EET and14,15-EEZE separately or in combination.Cell proliferation and apoptosis were analyzed using MTT assay and flow cytometry respectively.The expressions of p-AKT and p-FoxO1were determined by Western blot.Results The flow cytometry results showed that H9c2cells apoptosis rate increased by PA pretreatment which can be reversed by14,15-EET.This protection was partially abolished by14,15-EEZE which by itself enhanced PA induced apoptosis.Western blot showed that the phosphorylation of AKT and FoxO1was down-regulated by PA and up-regulated by14,15-EET in H9c2cell.14,15-EEZE reduced phosphorylate AKT and FoxO1levels elevated by14,15-EET.Conclusion14,15-EET inhibited PA induced apoptosis in H9c2cells through the activation of AKT/FoxO1pathway.14,15-EEZE abolished such protection through inhibiting AKT/FoxO1pathway.

关 键 词：棕榈酸 14  15-EET 14  15-EEZE H9C2 细胞 凋亡 

分 类 号：R544.1[医药卫生—心血管疾病]