|本期目录/Table of Contents|

[1]吕瑾 杨胜祥 华晓芳 刘长召.黑芥子苷通过p38/JNK MAPK信号通路对阿霉素心脏毒性的保护作用[J].国际心血管病杂志,2020,01:48-51.
 Lv Jin,YANG Shengxiang,HUA Xiaofang,et al.Sinigrin protects against doxorubicin-induced cardiotoxicity via the p38/JNK MAPK pathway[J].International Journal of Cardiovascular Disease,2020,01:48-51.
点击复制

黑芥子苷通过p38/JNK MAPK信号通路对阿霉素心脏毒性的保护作用(PDF)

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

期数:
2020年01期
页码:
48-51
栏目:
基础研究
出版日期:
2020-01-14

文章信息/Info

Title:
Sinigrin protects against doxorubicin-induced cardiotoxicity via the p38/JNK MAPK pathway
作者:
吕瑾 杨胜祥 华晓芳 刘长召
445000恩施土家族苗族自治州中心医院心血管内科
Author(s):
Lv Jin YANG Shengxiang HUA Xiaofang LIU Changzhao
Department of Cardiology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei445000, China
关键词:
阿霉素 心脏毒性 黑芥子苷 凋亡 信号通路
Keywords:
Doxorubicin Cardiotoxicity Sinigrin Apoptosis Signaling pathway
分类号:
-
DOI:
10.3969/j.issn.1673-6583.2020.01.012
文献标识码:
-
摘要:
目的:探讨黑芥子苷对阿霉素诱导的心脏毒性的作用及机制。方法:10周龄雄性C57/BL6小鼠随机分为对照组、黑芥子苷组、阿霉素组和黑芥子苷+阿霉素组。阿霉素组和黑芥子苷+阿霉素组给予单次腹腔注射阿霉素(15 mg/kg),对照组和黑芥子苷组给予单次腹腔注射生理盐水(15 mg/kg),黑芥子苷组和黑芥子苷+阿霉素组小鼠同时用黑芥子苷5 mg/kg灌胃,每2天1次,共3次。7 d后超声心动图检测心脏功能,Western blot检测心肌中凋亡相关蛋白和MAPK信号通路相关蛋白的表达水平。结果:黑芥子苷组与对照组小鼠超声心动图各指标、凋亡相关蛋白表达水平和MAPK相关蛋白表达水平的差异无统计学意义。与对照组相比,阿霉素组小鼠LVEDD、LVESD均明显增大,LVEF和LVFS均明显减小,Bax表达水平、p38和JNK的磷酸化水平明显升高,Bcl-2表达水平明显降低(P均<0.05)。与阿霉素组相比,黑芥子苷+阿霉素组小鼠LVEDD、LVESD均明显减小,LVEF和LVFS均明显增大,Bax表达水平、p38和JNK的磷酸化水平均明显降低,Bcl-2表达水平明显升高(P均<0.05)。结论:黑芥子苷通过p38/JNK MAPK信号通路减少心肌细胞凋亡,减轻阿毒素诱导的心脏毒性。
Abstract:
Objective:To investigate the effect and mechanism of sinigrin on doxorubicin-induced cardiotoxicity.Methods:Male C57/BL mice aged 10 weeks were randomly divided into control group, sinigrin group, doxorubicin group and sinigrin+doxorubicin group. A single intraperitoneal injection of doxorubicin(15 mg/kg)was given to mice in the doxorubicin group and the sinigrin+doxorubicin group. While in the control group and the mycosidin group, a single intraperitoneal injection of saline(15 mg/kg)was given. At the same time mice in the sinigrin group and the sinigrin+doxorubicin group were intragastrically administered with sinigrin 5 mg/kg once every 2 days, 3 times in total. After 7 days, cardiac function was evaluated by echocardiography, and the expression levels of apoptosis-related proteins and MAPK signaling pathway-related proteins in myocardium were detected by western blot.Results:There were no significant statistical differences in the echocardiographic indicators, expression of apoptosis-related proteins and MAPK-related proteins between the sinigrin group and the control group. Compared with the control group, LVEDD and LVESD were significantly larger, LVEF and LVFS were significantly smaller; Bax expression level, phosphorylation levels of P38 and JNK were significantly higher, and Bcl-2 expression level was significantly lower, in the doxorubicin group(P all<0.05). Compared with the doxorubicin group, LVEDD and LVESD were significantly smaller in the sirolimus+doxorubicin group, and LVEF and LVFS were significantly larger; Bax expression level, phosphorylation levels of P38 and JNK were significantly lower, while Bcl-2 expression levels were significantly higher(P all <0.05).Conclusions:Sinigrin reduces the cardiomyocyte apoptosis through P38/JNK MAPK signaling pathway and protects against doxorubicin-induced cardiotoxicity.

参考文献/References

[ 1 ]Abdel-Raheem IT, Omran GA, Katary MA. Irbesartan, an angiotensin Ⅱ receptor antagonist, with selective PPAR-gamma-modulating activity improves function and structure of chemotherapy-damaged ovaries in rats[J]. Fundam Clin Pharmacol, 2015, 29(3):286-298.
[ 2 ]Akolkar G, Bhullar N, Bews H, et al. The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity[J]. Cardiovasc Ultrasound, 2015, 13:18.
[ 3 ]Carvalho FS, Burgeiro A, Garcia R, et al. Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy[J]. Med Res Rev, 2014, 34(1):106-135.
[ 4 ]Damiani RM, Moura DJ, Viau CM, et al. Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone[J]. Arch Toxicol, 2016, 90(9):2063-2076.
[ 5 ]Bahadr A, Kurucu N, Kadog¨lu M, et al. The role of nitric oxide in Doxorubicin-induced cardiotoxicity: experimental study[J]. Turk J Haematol, 2014, 31(1):68-74.
[ 6 ]Zhao L, Tao X, Qi Y, et al. Protective effect of dioscin against doxorubicin-induced cardiotoxicity via adjusting microRNA-140-5p-mediated myocardial oxidative stress[J]. Redox Biol, 2018, 16:189-198.
[ 7 ]Chen CT, Wang ZH, Hsu CC, et al. In vivo protective effects of diosgenin against Doxorubicin-induced cardiotoxicity[J]. Nutrients, 2015, 7(6):4938-4954.
[ 8 ]Lee HW, Lee CG, Rhee DK, et al. Sinigrin inhibits production of inflammatory mediators by suppressing NF-κB/MAPK pathways or NLRP3 inflammasome activation in macrophages[J]. Int Immunopharmacol, 2017,45:163-173.
[ 9 ]Lozano-Baena MD, Tasset I, Obregón-Cano S, et al. Antigenotoxicity and tumor growing inhibition by leafy brassica carinata and sinigrin[J]. Molecules, 2015, 20(9):15748-15765.
[10]Mazumder A, Dwivedi A, Du Plessis J. Sinigrin and its therapeutic benefits[J]. Molecules, 2016, 21(4):416.
[11]Jang YJ, Park B, Lee HW, et al. Sinigrin attenuates the progression of atherosclerosis in ApoE-/- mice fed a high-cholesterol diet potentially by inhibiting VCAM-1 expression[J]. Chem Biol Interact, 2017, 272:28-36.
[12]Mitry MA, Edwards JG. Doxorubicin induced heart failure: phenotype and molecular mechanisms[J]. Int J Cardiol Heart Vasc, 2016, 10:17-24.
[13]Wang Y, Lei T, Yuan J, et al. GCN2 deficiency ameliorates doxorubicin-induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress[J]. Redox Biol, 2018, 17:25-34.
[14]Sun J, Sun G, Meng X, et al. Isorhamnetin protects against doxorubicin-induced cardiotoxicity in vivo and in vitro[J]. PLoS One, 2013, 8(5):e64526.
[15]Lee BS, Kim SH, Jin T, et al. Protective effect of survivin in doxorubicin-induced cell death in h9c2 cardiac myocytes[J]. Korean Circ J, 2013, 43(6):400-407.
[16]Abdel-Raheem IT, Taye A, Abouzied MM. Cardioprotective effects of nicorandil, a mitochondrial potassium channel opener against doxorubicin-induced cardiotoxicity in rats[J]. Basic Clin Pharmacol Toxicol, 2013, 113(3):158-166.
[17]Gharanei M, Hussain A, Janneh O, et al. Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore[J]. Toxicol Appl Pharmacol, 2013, 268(2):149-156.
[18]Ahmed LA, El-Maraghy SA. Nicorandil ameliorates mitochondrial dysfunction in doxorubicin-induced heart failure in rats: possible mechanism of cardioprotection[J]. Biochem Pharmacol, 2013, 86(9):1301-1310.
[19]Das J, Ghosh J, Manna P, et al. Taurine suppresses doxorubicin-triggered oxidative stress and cardiac apoptosis in rat via up-regulation of PI3-K/Akt and inhibition of p53, p38-JNK[J]. Biochem Pharmacol, 2011, 81(7):891-909.

备注/Memo

备注/Memo:
作者单位:445000恩施土家族苗族自治州中心医院心血管内科
通信作者:刘长召,E-mail:372465257@qq.com
更新日期/Last Update: 2020-01-15