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选用Wistar雄性大鼠49只,随机分为对照组17只,每周阿霉素2mg/kg;用药3周者13只(ADR_3组);6周者10只(ADR~6组);10周者9只(ADR_(10)组),末次注射后间隔一周处死动物并取材。大体解剖表明对照组及ADR_3组正常;ADR_0组3只有腹水;ADR_(10)组7只有心包积液、胸水、腹水,提示心力衰竭。超微结构显示对照组及ADR_3组基本正常;APD_6及ADR_(10)有明显异常,细胞内水肿,染色质块状凝集,肌丝排列紊乱、溶解、断裂,线粒体肿胀、嵴断裂、空泡变、膜破裂等。电生理、快反应动作电位是ADR_6和ADR_(10)两组的ADR_(50)明显延长(P<0.05),慢反应动作电位ADR_6和ADR_(10)两组的APD_(50)、APD_(90)明显延长,V_(max)明显增加(P<0.05),其他电生理参数无明显改变。结果提示心肌细胞电生理和超微结构的变化与药物累积剂量相关。毒性反应与增加心肌细胞钙内流有关。
A total of 49 Wistar male rats were randomly divided into control group (n = 17), adriamycin 2 mg / kg weekly for 3 weeks, ADR group (n = 3) (ADR_ (10) group). Animals were sacrificed and sacrificed one week after the last injection. The gross anatomy showed that the control group and the ADR_3 group were normal; 3 ascites in ADR_0 group; 7 pericardial effusion, pleural effusion and ascites in ADR_ (10) group, suggesting heart failure. The ultrastructure showed that the control group and ADR_3 group were basically normal. There were obvious abnormalities of APD_6 and ADR_ (10), intracellular edema, massive agglutination of chromatin, disordered myofilament, dissolution, rupture, swelling of mitochondria, , Membrane rupture and the like. The electrophysiological and rapid response potentials of ADR_6 and ADR_ (10) groups were significantly prolonged (P <0.05), APD_ (50) and APD_ (90) of ADR_6 and ADR_ (10) ) Was significantly prolonged, V max significantly increased (P <0.05), other electrophysiological parameters did not change significantly. The results suggest that the changes of electrophysiological and ultrastructural changes in cardiomyocytes are related to the cumulative doses of drugs. Toxicity and increased calcium influx of myocardial cells.