|本期目录/Table of Contents|

[1]俞健颖 潘建安 张俊峰 王长谦 顾俊.白藜芦醇对阿霉素诱导心肌细胞凋亡的保护作用及机制研究[J].国际心血管病杂志,2019,06:341-345.
 YU Jianying,PAN Jianan,ZHANG Junfeng,et al.Protective effect and mechanism of resveratrol on doxorubicin-induced cardiomyocyte apoptosis[J].International Journal of Cardiovascular Disease,2019,06:341-345.
点击复制

白藜芦醇对阿霉素诱导心肌细胞凋亡的保护作用及机制研究(PDF)

《国际心血管病杂志》[ISSN:1006-6977/CN:61-1281/TN]

期数:
2019年06期
页码:
341-345
栏目:
基础研究
出版日期:
2019-12-31

文章信息/Info

Title:
Protective effect and mechanism of resveratrol on doxorubicin-induced cardiomyocyte apoptosis
作者:
俞健颖 潘建安 张俊峰 王长谦 顾俊
200011 上海交通大学医学院附属第九人民医院心血管内科
Author(s):
YU Jianying PAN Jianan ZHANG Junfeng WANG Changqian GU Jun
Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
关键词:
阿霉素 心肌细胞 凋亡 E2F转录因子1 白藜芦醇
Keywords:
Doxorubicin Cardiomyocyte Apoptosis E2F transcription factor 1 Resveratrol
分类号:
-
DOI:
10.3969/j.issn.1673-6583.2019.06.006
文献标识码:
-
摘要:
目的:探讨白藜芦醇(RSV)对阿霉素诱导的心肌细胞凋亡的保护作用及对E2F转录因子1(E2F1)/腺苷酸活化蛋白激酶α2(AMPKα2)信号通路的影响。方法:用小干扰RNA siE2F1转染H9c2心肌细胞,将H9c2细胞分为对照组、阿霉素组、siE2F1组、阿霉素+siE2F1组、RSV组、阿霉素+RSV组,阿霉素终浓度为1 μmol/L,RSV终浓度为20 μmol/L。各组干预24 h后,检测E2F1、AMPKα2和胱天蛋白酶-3剪切体(cleaved caspase-3)的蛋白表达水平及心肌细胞凋亡率。结果:与对照组相比,阿霉素组E2F1、AMPKα2和cleaved caspase-3的蛋白表达水平和心肌细胞凋亡率均显著增加(P均<0.001)。细胞转染后,siE2F1显著抑制E2F1的表达。与阿霉素组相比,阿霉素+siE2F1组E2F1、AMPKα2和cleaved caspase-3的蛋白表达水平及心肌细胞凋亡率显著降低(P均<0.001)。RSV干预能够部分逆转阿霉素诱导的心肌细胞凋亡(P<0.001),与阿霉素组相比,阿霉素+RSV组E2F1、AMPKα2和cleaved caspase-3的蛋白表达水平显著降低(P均<0.001)。结论:RSV可减轻阿霉素诱导的心肌细胞凋亡,其机制可能与抑制E2F1/AMPKα2通路的激活有关。
Abstract:
Objective:To investigate the effects of resveratrol(RSV)on doxorubicin(DOX)-induced cardiomyocyte apoptosis and E2F transcription factor 1(E2F1)/AMP-activated protein kinase α2(AMPKα2)signaling pathway.Methods:A small interfering RNA siE2F1 was used to transfect the rat cardiomyocyte cell line(H9c2). H9c2 cells were divided into six groups: control group, DOX group, siE2F1 group, DOX+siE2F1 group, RSV group and DOX+RSV group. The final concentration of DOX and RSV were 1 μmol/L and 20 μmol/L, respectively. Expression of E2F1, AMPKα2, cleaved caspase-3 and the apoptosis rate of cardiomyocytes were detected at 24 hours after intervention in each group.Results:Compared with the control group, the expression of E2F1, AMPKα2, cleaved caspase-3 and the apoptosis rate of cardiomyocytes significantly increased in the DOX group(P all<0.001). After transfection, siE2F1 significantly inhibited the expression of E2F1. Compared with the DOX group, the expression of E2F1, AMPKα2, cleaved caspase-3 and the apoptosis rate of cardiomyocytes in DOX+siE2F1 group significantly decreased(P all<0.001). RSV partially reversed the apoptosis of cardiomyocytes induced by DOX(P<0.001). The expression of E2F1, AMPKα2 and cleaved caspase-3 significantly decreased in RSV+DOX group compared with the DOX group(P all<0.001).Conclusions:RSV can attenuate DOX-induced cardiomyocyte apoptosis, and its mechanism may be related to the inhibition of E2F1/AMPKα2 pathway activation.

参考文献/References

[ 1 ] Lipshultz SE, Miller TL, Lipsitz SR, et al. Continuous versus bolus infusion of doxorubicin in children with ALL: long-term cardiac outcomes[J]. Pediatrics, 2012, 130(6):1003-1011.
[ 2 ] Lipshultz SE, Scully RE, Lipsitz SR, et al. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial[J]. Lancet Oncol, 2010, 11(10):950-961.
[ 3 ] Lipshultz SE, Miller TL, Scully RE, et al. Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes[J]. J Clin Oncol, 2012, 30(10):1042-1049.
[ 4 ] Von Hoff DD, Rozencweig M, Layard M, et al. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases[J]. Am J Med, 1977, 62(2):200-208.
[ 5 ] Zhang S, Liu X, Bawa-Khalfe T, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity[J]. Nat Med, 2012, 18(11):1639-1642.
[ 6 ] Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities[J]. J Am Coll Cardiol, 2014, 64(9):938-945.
[ 7 ] Iaquinta PJ, Lees JA. Life and death decisions by the E2F transcription factors[J]. Curr Opin Cell Biol, 2007, 19(6):649-657.
[ 8 ] Meo-Evoli N, Almacellas E, Massucci FA, et al. V-ATPase: a master effector of E2F1-mediated lysosomal trafficking, mTORC1 activation and autophagy[J]. Oncotarget, 2015, 6(29):28057-28070.
[ 9 ] Yang W, Park IJ, Yun H, et al. AMP-activated protein kinase α2 and E2F1 transcription factor mediate doxorubicin-induced cytotoxicity by forming a positive signal loop in mouse embryonic fibroblasts and non-carcinoma cells[J]. J Biol Chem, 2014, 289(8):4839-4852.
[10] Huang XT, Li X, Xie ML, et al. Resveratrol: review on its discovery, anti-leukemia effects and pharmacokinetics[J]. Chem Biol Interact, 2019, 306:29-38.
[11] Gu J, Hu W, Song ZP, et al. Resveratrol-induced autophagy promotes survival and attenuates doxorubicin-induced cardiotoxicity[J]. Int Immunopharmacol, 2016, 32:1-7.
[12] Gu J, Hu W, Zhang DD. Resveratrol, a polyphenol phytoalexin, protects against doxorubicin-induced cardiotoxicity[J]. J Cell Mol Med, 2015, 19(10):2324-2328.
[13] Movahed A, Yu L, Thandapilly SJ, et al. Resveratrol protects adult cardiomyocytes against oxidative stress mediated cell injury[J]. Arch Biochem Biophys, 2012, 527(2):74-80.
[14] Rivankar S. An overview of doxorubicin formulations in cancer therapy[J]. J Cancer Res Ther, 2014, 10(4):853-858.
[15] Wenningmann N, Knapp M, Ande A, et al. Insights into doxorubicin-induced cardiotoxicity: molecular mechanisms, preventive strategies, and early monitoring[J]. Mol Pharmacol, 2019, 96(2):219-232.
[16] Gu J, Song ZP, Gui DM, et al. Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in lymphoma nude mice by heme oxygenase-1 induction[J]. Cardiovasc Toxicol, 2012, 12(4):341-349.
[17] Wang X, Wang XL, Chen HL, et al. Ghrelin inhibits doxorubicin cardiotoxicity by inhibiting excessive autophagy through AMPK and p38-MAPK[J]. Biochem Pharmacol, 2014, 88(3):334-350.
[18] Gao S, Li H, Feng XJ, et al. α-Enolase plays a catalytically independent role in doxorubicin-induced cardiomyocyte apoptosis and mitochondrial dysfunction[J]. J Mol Cell Cardiol, 2015, 79:92-103.
[19] Sun A, Cheng Y, Zhang Y, et al. Aldehyde dehydrogenase 2 ameliorates doxorubicin-induced myocardial dysfunction through detoxification of 4-HNE and suppression of autophagy[J]. J Mol Cell Cardiol, 2014, 71:92-104.
[20] Denechaud PD, Fajas L, Giralt A. E2F1, a novel regulator of metabolism[J]. Front Endocrinol, 2017, 8:311.
[21] Jiang H, Martin V, Gomez-Manzano C, et al. The RB-E2F1 pathway regulates autophagy[J]. Cancer Res, 2010, 70(20):7882-7893.
[22] Mohammadshahi M, Haidari F, Soufi FG. Chronic resveratrol administration improves diabetic cardiomyopathy in part by reducing oxidative stress[J]. Cardiol J, 2014, 21(1):39-46.
[23] Usta E, Mustafi M, Walker T, et al. Resveratrol suppresses apoptosis in intact human cardiac tissue—in vitro model simulating extracorporeal circulation[J]. J Cardiovasc Surg(Torino), 2011, 52(3):399-409.
[24] Moreira AC, Branco AF, Sampaio SF, et al. Mitochondrial apoptosis-inducing factor is involved in doxorubicin-induced toxicity on H9c2 cardiomyoblasts[J]. Biochim Biophys Acta, 2014, 1842(12 Pt A):2468-2478.
[25] Zhang C, Feng Y, Qu S, et al. Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53[J]. Cardiovasc Res, 2011, 90(3):538-545.
[26] Tan Y, Wei X, Zhang W, et al. Resveratrol enhances the radiosensitivity of nasopharyngeal carcinoma cells by downregulating E2F1[J]. Oncol Rep, 2017, 37(3):1833-1841.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金(81670293)
作者单位:200011 上海交通大学医学院附属第九人民医院心血管内科
通信作者:顾俊,Email:gjforsub@163.com
更新日期/Last Update: 2019-12-27