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

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。

Sinigrin protects against doxorubicin-induced cardiotoxicity via the p38/JNK MAPK pathway

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.