论文部分内容阅读
目的：探讨柔红霉素（ DNR）致大鼠心肌损伤的作用机制。方法用随机数字表法将健康清洁的SD大鼠分为DNR组和对照组，每组20只。DNR组腹腔注射DNR 3.5 mg/kg，对照组腹腔注射等容积0.9%氯化钠注射液，均每周1次，连续4周。注射DNR或0.9%氯化钠注射液1、3和4周末2组分别各取5只大鼠进行心电图、心肌组织肌浆网Ca2﹢-ATP酶（ SERCA2a）蛋白表达及组织病理学检测。结果腹腔注射DNR可成功复制亚急性心肌损伤大鼠模型。实验第2周时DNR组大鼠出现精神差、活动缓慢、嗜睡、进食减少等症状，对照组大鼠活动、体重、进食均正常；第4周大鼠心电图QRS波电压下降>30%，ST段抬高，P波尖耸，心肌组织病理学检查显示心肌细胞胞质浑浊，有空泡形成，肌纤维排列紊乱，间隔增宽。实验1周时2组大鼠心肌组织SERCA2a蛋白表达均呈中等阳性，而实验3及4周末DNR组大鼠心肌组织SERCA2a蛋白表达均呈弱阳性。实验3及4周末，DNR组大鼠SERCA2a蛋白表达阳性细胞数明显低于同时点对照组大鼠[（42.2±1.2）个比（65.30±1.6）个，（35.2±6.0）个比（66.7±1.5）个，均P﹤0.05]。结论 DNR可抑制大鼠心肌组织SERCA2a蛋白表达，可能是其心肌毒性的机制之一。“,”Objective To explore the mechanism of in myocardial damage due to daunorubicin (DNR)in rats. Methods SD rats were divided into the control group and the DNR group using a random-digital table,each group comprised 15 rats. The rats in the DNR group received intraperitoneal injection of daunorubicin 3. 5 mg/kg once a week for 4 weeks. The rats in the control group received intraperitoneal injection of same volume of 0. 9% sodium chloride solution once a week for 4 weeks. The rats′behavior changes in the 2 groups were observed. The electrocardiographic examination,expression of sarcoplasmic reticulum Ca2﹢-ATP enzyme( SERCA2a)and histopathological test were performed at the end of 1,3 and 4 weeks of the experiment on 5 rats in the 2 groups,respectively. Results The subacute myocardial injury rat model could be reproduced by DNR intraperitoneal injection. The rats in the DNR group developed lassitude,drumble and drowsiness from the second week. The control group rats′activity, body weight and feeding were normal. The electrocardiographic examination in DNR group showed the following results:voltage of QRS wave decreased by more than 30% compared with the normal,ST segment elevation,and P wave peaked. Myocardial tissue histopathological examination revealed turbid cytoplasm, vacuolation,disordered arrangement of muscle fiber,and broadened fiber gaps. The expression of SERCA2a were moderately positive in both groups at the end of the first week. The expression of SERCA2a were weakly positive in the DNR group at the end of the third and fourth weeks. The number of SERCA2a positive cells in the DNR group at the end of the third and fourth weeks was significantly less than that in the control group at the same time points[(42. 2 ± 1. 2)vs(65. 30 ± 1. 6),(35. 2 ± 6. 0)vs(66. 7 ± 1. 5),all P﹤0. 05]. Conclusion DNR may inhibit the expression of SERCA2a in myocardial tissue and it may be one of the mechanisms of DNR′s myocardial toxicity.