果胶阿霉素对大鼠心脏毒性的研究

Study of pectin-adriamycin conjugate to cardiac toxicity in rats

目的考察果胶阿霉素(PAC)对大鼠心脏毒性的影响。方法 50只大鼠随机分成5组,每组10只。阿霉素(ADM)组腹腔注射3 mg·kg^(-1),隔天给药1次,连续给药6次;PAC组分别腹腔注射ADM当量1.5、3、6 mg·kg^(-1),隔天给药1次,连续给药6次;对照组腹腔注射生理盐水3 mg·kg^(-1),隔天给药1次,连续给药6次。给药后48 h处死大鼠,检测大鼠超声心动图、心肌酶、心脏组织中氧化应激水平及心脏组织病理学的变化。同时建立S180腹水瘤模型,检测PAC的抗肿瘤作用。结果 ADM组大鼠存活率为50%,PAC各组大鼠存活率为100%;PAC能不同程度增加大鼠体重、心脏指数及免疫指数;增加HR、EF、FS,减小LVIDd、LVIDs;降低血清中AST、LDH、CK、CK-MB活性;增加心肌组织中GSH-Px、SOD活性,降低MDA含量;改善病理学变化;PAC能明显降低腹水的生长,延长小鼠生存期。结论 PAC能有效改善心脏毒性,提高大鼠存活率,改善免疫能力及心功能,改善心肌酶和氧化应激,减少心肌细胞损伤,而且有明显的抗肿瘤作用。

Aim To study the effect of pectin-adriamycinconjugate （ PAC ） on cardiac toxicity Methods 50female SD rats were randomly divided into 5 groupswith 10 animals in each group. Adriamycin （ADM ）group received 3 mg·kg^-1, ip,every other day for 6times. PAC group received ADM equivalent 1. 5,3 and6 mg·kg^-1, ip,every other day for 6 times. Controlgroup received normal saline parallel to ADM . Ratswere sacrificed and the echocardiogram, cardiac enzymes,the oxidative stress levels in myocardial cellsand histopathological changes after 48 h administrationwere detected. SI80 ascites tumor bearing mice modelswere established to investigate the antitumor activity of PAC . Results The survival rate of ADM group was50 % and that of PAC each group was 100 % . PACcould significantly increase body weight,heart index andimmune index and increase HR ,EF ,FS ,reduce LVID d,LVIDs. PAC could also significantly increase the AST ,LDH ,CK , CK-MB level in serum. GSH-Px and SO Dactivities of PAC gou p were significantly increased and MDA contents were reduced, and histopathologicalchanges decreased . PAC could effectively inhibit the growth of tumor cells and extend the survival period ofmice. Conclusion PAC induces a significant reductionin cardiotoxicity by increasing survival rate, immune and cardiac function, improving cardiac enzymes,oxidative stress and myocardial cell injury,andalso PAC has obvious antitumor effect.