药物不良反应杂志
藥物不良反應雜誌
약물불량반응잡지
ADVERSE DRUG REACTIONS JOURNAL
2014年
3期
159-162
,共4页
罗玲娟%谢新梅%何文婷%曾凡业%张洪亮
囉玲娟%謝新梅%何文婷%曾凡業%張洪亮
라령연%사신매%하문정%증범업%장홍량
柔红霉素%肌浆网钙转运ATP酶类%大鼠
柔紅黴素%肌漿網鈣轉運ATP酶類%大鼠
유홍매소%기장망개전운ATP매류%대서
Daunorubicin%Sarcoplasmic reticulum calcium-transporting ATPases%Rats
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。
目的：探討柔紅黴素（ DNR）緻大鼠心肌損傷的作用機製。方法用隨機數字錶法將健康清潔的SD大鼠分為DNR組和對照組，每組20隻。DNR組腹腔註射DNR 3.5 mg/kg，對照組腹腔註射等容積0.9%氯化鈉註射液，均每週1次，連續4週。註射DNR或0.9%氯化鈉註射液1、3和4週末2組分彆各取5隻大鼠進行心電圖、心肌組織肌漿網Ca2﹢-ATP酶（ SERCA2a）蛋白錶達及組織病理學檢測。結果腹腔註射DNR可成功複製亞急性心肌損傷大鼠模型。實驗第2週時DNR組大鼠齣現精神差、活動緩慢、嗜睡、進食減少等癥狀，對照組大鼠活動、體重、進食均正常；第4週大鼠心電圖QRS波電壓下降>30%，ST段抬高，P波尖聳，心肌組織病理學檢查顯示心肌細胞胞質渾濁，有空泡形成，肌纖維排列紊亂，間隔增寬。實驗1週時2組大鼠心肌組織SERCA2a蛋白錶達均呈中等暘性，而實驗3及4週末DNR組大鼠心肌組織SERCA2a蛋白錶達均呈弱暘性。實驗3及4週末，DNR組大鼠SERCA2a蛋白錶達暘性細胞數明顯低于同時點對照組大鼠[（42.2±1.2）箇比（65.30±1.6）箇，（35.2±6.0）箇比（66.7±1.5）箇，均P﹤0.05]。結論 DNR可抑製大鼠心肌組織SERCA2a蛋白錶達，可能是其心肌毒性的機製之一。
목적：탐토유홍매소（ DNR）치대서심기손상적작용궤제。방법용수궤수자표법장건강청길적SD대서분위DNR조화대조조，매조20지。DNR조복강주사DNR 3.5 mg/kg，대조조복강주사등용적0.9%록화납주사액，균매주1차，련속4주。주사DNR혹0.9%록화납주사액1、3화4주말2조분별각취5지대서진행심전도、심기조직기장망Ca2﹢-ATP매（ SERCA2a）단백표체급조직병이학검측。결과복강주사DNR가성공복제아급성심기손상대서모형。실험제2주시DNR조대서출현정신차、활동완만、기수、진식감소등증상，대조조대서활동、체중、진식균정상；제4주대서심전도QRS파전압하강>30%，ST단태고，P파첨용，심기조직병이학검사현시심기세포포질혼탁，유공포형성，기섬유배렬문란，간격증관。실험1주시2조대서심기조직SERCA2a단백표체균정중등양성，이실험3급4주말DNR조대서심기조직SERCA2a단백표체균정약양성。실험3급4주말，DNR조대서SERCA2a단백표체양성세포수명현저우동시점대조조대서[（42.2±1.2）개비（65.30±1.6）개，（35.2±6.0）개비（66.7±1.5）개，균P﹤0.05]。결론 DNR가억제대서심기조직SERCA2a단백표체，가능시기심기독성적궤제지일。
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.
