儿茶素对亚砷酸钠诱导心肌毒性的保护作用
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摘要
目的本研究旨在探讨儿茶素(epigallocatechin gllate,EGCG)对亚砷酸钠(NaAsO_2,As)诱导大鼠心肌细胞毒性的影响。方法动物试验:100只雄性SD大鼠随机分为5组,分别为对照组(control,n=20)、As模型组(As 10 mg/kg,n=20)、低剂量组(As10 mg/kg+EGCG 25 mg/kg,n=20)、高剂量组(As 10 mg/kg+EGCG 50 mg/kg,n=20)、维生素E(VE)组(As10 mg/kg+VE 75 mg/kg,n=20)。HE染色观察心肌组织的病理改变,透射电镜观察心肌组织超微结构改变,ELISA法检测心肌酶肌酸激酶(CK)、同工酶(CK-MB);比色法测定乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)。细胞实验:Hoechst33258染色检测心肌细胞凋亡。结果 As暴露引起大鼠心肌组织出现灶状坏死,部分心肌细胞变性,心肌超微结构损伤,CK、CK-MB、LDH活性增强及MDA含量升高,心肌SOD、CAT、GSH-Px活性降低。心肌细胞凋亡数目增加,EGCG作用后拮抗NaAsO_2所致上述变化。结论儿茶素可能对亚砷酸钠诱导的心肌毒性有保护作用,其机制可能通过抑制氧化应激和心肌细胞凋亡实现。
Objective This study was aimed to investigate the effects of EGCG on NaAsO_2-induced cardiotoxicity in rat hearts and H9c2 cells. Methods One hundred rats were randomly divided into five groups: normal control group( control,n = 20),As group( NaAsO_2,10 mg/kg,n = 20),low dosage of EGCG group( As 10 mg/kg+ EGCG 25 mg/kg,n = 20),high dosage of EGCG group( As 10 mg/kg + EGCG 50 mg/kg,n = 20) and VE group( As 10 mg/kg + VE 75 mg/kg,n = 20). The pathological changes of myocardial tissue were observed by HE staining. Cardiac ultrastructural changes were investigated by transmission electron( TEM). The activities of myocardial enzymes,the content of MDA and the activities of SOD,CAT,GSH-Px in myocardium were measured. Apoptosis of myocardial cells was detected by Hoechst33258 staining. Results Exposure to NaAsO_2 obviously caused necrosis and myocardial cell degeneration,injured myocardial ultrastructure damage,increased the activities of CK,CK-MB,LDH and the content of MDA,decreased the activities of SOD,CAT,GSH-Px. Compared with NaAsO_2 group,EGCG could prevent the alterations of the above-mentioned indexes. Conclusions These results suggested that EGCG may be a promising cardioprotective-agent against NaAsO_2-induced cardiotoxicity,at least in part,mediated through inhibition of cardiac apoptosis and oxidative stress.
Objective This study was aimed to investigate the effects of EGCG on NaAsO_2-induced cardiotoxicity in rat hearts and H9c2 cells. Methods One hundred rats were randomly divided into five groups: normal control group( control,n = 20),As group( NaAsO_2,10 mg/kg,n = 20),low dosage of EGCG group( As 10 mg/kg+ EGCG 25 mg/kg,n = 20),high dosage of EGCG group( As 10 mg/kg + EGCG 50 mg/kg,n = 20) and VE group( As 10 mg/kg + VE 75 mg/kg,n = 20). The pathological changes of myocardial tissue were observed by HE staining. Cardiac ultrastructural changes were investigated by transmission electron( TEM). The activities of myocardial enzymes,the content of MDA and the activities of SOD,CAT,GSH-Px in myocardium were measured. Apoptosis of myocardial cells was detected by Hoechst33258 staining. Results Exposure to NaAsO_2 obviously caused necrosis and myocardial cell degeneration,injured myocardial ultrastructure damage,increased the activities of CK,CK-MB,LDH and the content of MDA,decreased the activities of SOD,CAT,GSH-Px. Compared with NaAsO_2 group,EGCG could prevent the alterations of the above-mentioned indexes. Conclusions These results suggested that EGCG may be a promising cardioprotective-agent against NaAsO_2-induced cardiotoxicity,at least in part,mediated through inhibition of cardiac apoptosis and oxidative stress.
引文
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[2]Ireneusz L,Tomasz B,Dorota D,et al.Oxidative stress and replication-independent DNA breakage induced by arsenic in saccharomyces cerevisiae[J].Plos Genet,2013,9(7):e1003640.
[3]Zhao X Y,Li G Y,Liu Y,et al.Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo[J].British Journal of Pharmacology,2008,154(1):105-113.
[4]Zeng X,Li Q,Zhang M,et al.Green tea may be benefit to the therapy of atrial fibrillation[J].J Cell Biochem,2011,112(7):1709-1712.
[5]Balentine D A,Wiseman S A,Bouwens L C.The chemistry of tea flavonoids[J].Crit Rev Food Sci Nutr,1997,37(3):693-704.
[6]Jiang Z S,Xia C F,Tian Q P,et al.Effect of batroxobin against dog heart ischemia/reperfusion injury[J].Acta Pharmacol Sin,2000,21(1):70-74.
[7]Higaki Y,Mikami T,Fujii N,et al.Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway[J].Am J Physiol Endocrinol Metab,2008,294(5):889-897.
[8]Katherine M,Eliseo G,Ana N A.Arsenic Exposure and cardiovascular disease:an updated systematic review[J].Curr Atheroscler Rep,2012,14(6):542-555.
[9]Pouyssegur J,Mechta-Grigoriou F.Redox regulation of the hypoxia-inducible factor[J].Biol Chem,2006,387(10/11):1337-1346.
[10]Bharathi,Ravid R,Rao K S.Role of metals in neuronal apoptosis:challenges associated with neurodegeneration[J].Curr Alzheimer Res,2006,3(4):311-326.
[11]Francesca F,Liliana C,Fabrizio B,et al.Arsenic-induced genotoxicity and genetic susceptibility to arsenicrelated pathologies[J].Int J Environ Res Public Health,2013,10(4):1527-1546.
[12]李远慧,金婷婷.bcl-2 bax在砷中毒大鼠肾近端小管表达[J].中国公共卫生,2011,27(7):881-883.
[13]Joydeep D,Jyotirmoy G,Prasenjit M,et al.Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCδ-JNK pathway[J].Plos One,2010,5(9):e12602.