促红细胞生成素衍生肽抑制自噬和凋亡减轻阿霉素诱发的心脏毒性

Helix B surface peptide alleviates doxorubicin-induced cardiotoxicity by inhibiting autophagy and apoptosis

目的探讨促红细胞生成素衍生肽(helix B surface peptide,HBSP)抑制阿霉素(doxorubicin,DOX)诱发心脏毒性的作用及对自噬的调控作用。方法36只C57BL/6小鼠随机分为3组(n=12):对照(control)组、DOX组和HBSP治疗DOX组(DOX+HBSP),其中DOX组和DOX+HBSP组小鼠单次腹腔注射DOX(15 mg/kg),DOX+HBSP组小鼠同时腹腔注射HBSP 30μg/(kg·d)连续7 d;观察心脏结构、功能、血清肌钙蛋白T(cTnT)含量以及Caspase-3、cytochrome C、cleaved Caspase-3、Caspase-9、LC3B、Beclin1、LAMP2和P62的表达。结果与control组相比,DOX组小鼠心脏+d P/d t和-d P/d t值明显降低(P<0.01),血清中cTnT含量增加(P<0.01),部分心肌纤维断裂、排列紊乱并出现空泡化,Caspase-3、cytochrome C、cleaved Caspase-3、Caspase-9表达显著增加(P<0.01),LC3BⅡ/LC3BⅠ比值以及Beclin1和P62表达增加(P<0.01)。与DOX组比较,DOX+HBSP组心脏功能和结构明显改善(P<0.01),血清cTnT水平降低(P<0.01),Caspase-3、cytochrome C、cleaved Caspase-3、Caspase-9表达减少(P<0.01),LC3BⅡ/LC3BⅠ比值以及Beclin1和P62表达减少(P<0.01)。结论HBSP通过抑制细胞凋亡和自噬减轻阿霉素诱发的心脏毒性。

Objective To investigate the effect of helix B surface peptide(HBSP)on doxorubicin(DOX)-induced cardiotoxicity and its regulation effect on autophagy.Methods Thirty-six C57BL/6 mice were randomly divided into three groups(n=12):control group,DOX group and HBSP treatment group(DOX+HBSP).The mice were intraperitoneally injected with DOX(15 mg/kg)in DOX group and DOX+HBSP group.In addition,the mice in DOX+HBSP group were intraperitoneally injected with HBSP 30μg/(kg·d)for 7 d from the day of injection.Cardiac structure and function were observed,and the serum cTnT content,and the expression levels of Caspase-3,cytochrome C,cleaved Caspase-3,Caspase-9,LC3B,Beclin1,LAMP2 and P62 were detected.Results Compared with control group,the values of+d P/d t and-d P/d t were significantly decreased in DOX group(P<0.01),the serum cTnT content was increased(P<0.01),some myocardial fibers were broken,disordered and vacuolated,the expression levels of Caspase-3,cytochrome C,cleaved Caspase-3 and Caspase-9 were significantly increased(P<0.01),and the ratio of LC3BⅡ/LC3BⅠand the expression levels of Beclin1 and P62 were increased(P<0.01).Compared with DOX group,the cardiac structure and function were significantly improved in DOX+HBSP group,serum cTnT content was decreased(P<0.01),and the expression levels of Caspase-3,cytochrome C,cleaved Caspase-3,Caspase-9,LC3BⅡ/LC3BⅠratio,Beclin1 and P62 were decreased(P<0.01).Conclusion HBSP can attenuate the doxorubicin-induced cardiotoxicity by inhibiting apoptosis and autophagy.