CAJ | 학술논문

目的:研究Zn诱导金属硫蛋白(metallothionein,MT)表达对多柔比星(doxorubicin,DOX)心脏毒性的保护作用及其机制.方法:雄性C57/BL6J小鼠随机分成4组(n=6),即对照组(contro1)、给药组(DOX)、预处理组(Zn)、预处理给药组(Zn+DOX).动物单次腹腔注射DOX(20mg.kg-1)或等剂量的生理盐水(NS),此前24h及48h分别给予ZnSO4(300μmol·kg-1,sc)或等剂量的NS预处理.DOX给药后d4,测定血浆肌酸激酶(CK)及乳酸脱氢酶(LDH)活性;光学显微镜检查心脏组织形态学改变;测定心脏组织匀浆中MT、丙二醛(MDA)和还原型谷胱甘肽(GSH)含量以及谷胱甘肽过氧化物酶(GSHpx)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性并测定组织过氧化氢(H2O2)浓度.结果:与对照组相比,Zn能显著诱导心脏MT的过表达,而对CK、LDH、MDA、GSHpx、SOD、CAT、GSH、H2O2以及组织形态学无明显影响;给药组病理学检查可见心肌纤维浊肿、肌浆溶解、胞核淡染或固缩,CK、LDH及MDA升高,组织GSHpx、SOD活性及GSH含量显著下降,CAT活性及H2O2浓度升高;Zn预处理能显著抑制DOX诱导的心脏毒性效应,心脏毒性损伤明显减轻.提示Zn预处理诱导心脏MT过表达后,MT可作为体内有效的抗氧化物拮抗DOX心脏毒性.结论:Zn诱导MT表达对DOX心脏毒性具有明显的保护作用,其机制可能与MT体内清除自由基功能有关.
목적:연구Zn유도금속류단백(metallothionein,MT)표체대다유비성(doxorubicin,DOX)심장독성적보호작용급기궤제.방법:웅성C57/BL6J소서수궤분성4조(n=6),즉대조조(contro1)、급약조(DOX)、예처리조(Zn)、예처리급약조(Zn+DOX).동물단차복강주사DOX(20mg.kg-1)혹등제량적생리염수(NS),차전24h급48h분별급여ZnSO4(300μmol·kg-1,sc)혹등제량적NS예처리.DOX급약후d4,측정혈장기산격매(CK)급유산탈경매(LDH)활성;광학현미경검사심장조직형태학개변;측정심장조직균장중MT、병이철(MDA)화환원형곡광감태(GSH)함량이급곡광감태과양화물매(GSHpx)、초양화물기화매(SOD)、과양화경매(CAT)활성병측정조직과양화경(H2O2)농도.결과:여대조조상비,Zn능현저유도심장MT적과표체,이대CK、LDH、MDA、GSHpx、SOD、CAT、GSH、H2O2이급조직형태학무명현영향;급약조병이학검사가견심기섬유탁종、기장용해、포핵담염혹고축,CK、LDH급MDA승고,조직GSHpx、SOD활성급GSH함량현저하강,CAT활성급H2O2농도승고;Zn예처리능현저억제DOX유도적심장독성효응,심장독성손상명현감경.제시Zn예처리유도심장MT과표체후,MT가작위체내유효적항양화물길항DOX심장독성.결론:Zn유도MT표체대DOX심장독성구유명현적보호작용,기궤제가능여MT체내청제자유기공능유관.
AIM: To investigate the effects of metallothionein (MT) induced by zinc on doxorubicin (DOX)-treated mice and to explore the potential mechanisms. METHODS: Male C57BL/6J mice were divided randomly into 4 groups (n = 6) following control, DOX, Zn and Zn plus DOX. Mice were pretreated with eikg-1, ip) or equal volume of saline, and were killed on d 4 after the last injection. Serum and hearts were collected for examination. RESULTS: Zinc pretreatment elevated cardiac MT levels significantly while other antioxidants in heart including glutathione (GSH), glutathione peroxidase (GSHpx) , superoxide dismutase (SOD), and catalase (CAT) were not altered. Severe oxidative injury occurred in the mice treated with DOX as myocardial lipid peroxidation and morphological changes manifested by myocardial fibers swelling and vacuolization and nuclear condensation or dissolution, with increased activities of serum creatine kinase and lactate dehydrogenase and depletion of GSH, GSHpx, and SOD while CAT activity was increased in compensation. However, pre-induction of MT with zinc attenuated all of these toxic changes significantly. Furthermore, DOX induced elevation of hydrogen peroxide in heart tissues was greatly inhibited by zinc pretreatment. CONCLUSION: Preinduction of MT by zinc protects the heart from DOX-induced cardiotoxicity, and this effect is possibly correlated with the property of MT on scavenging free radicals in vivo.