MicroRNAs participate in the cardioprotective activity of dexrazoxane against doxorubicin-induced cardiotoxicity  

作　　者：符永恒 朱杰宁 黄帅 郭林林 林秋雄 张梦珍 谭虹虹 邝素娟 杨惠 费洪文 李文瑜 单志新 

机构地区：[1]Guangdong General Hospital,Guangdong Provincial Cardiovascular Institute [2]Guangdong Academy of Medical Sciences

出　　处：《South China Journal of Cardiology》2012年第3期169-179,196,共12页岭南心血管病杂志（英文版）

基　　金：supported by Grants from the National Natural Science Foundation of China (No. 81070102);Foundation of the Guangdong Provincial Science and Technology (20100309);the Natural Science Foundation of the Guangdong Province (Nos. 10151008004000035, S2011020005911)

摘　　要：Background The co-administration of dexrazoxane （DEX） with each dose of doxoruhicin （Dox） is an efficient strategy to relieve Dox-induced cardiotoxicity, however, the mechanisms underlying the cardioprotective effect of DEX have not been well elucidated. MieroRNAs （miRNAs） are endogenous, small non-coding RNAs that negatively regulate gene expression in diverse biological and pathological processes. The aim of the present study was to investigate whether the certain cardiac miRNAs were involved in DOX-induced cardiotoxicity. Methods Male SD rats were randomized into five groups, including the 4-week （cumulative dose： 16 mg/kg） and the 8-week （cumulative dose： 32 mg/kg） Dox-treated groups, and the corresponding 4-week and 8-week Dox plus DEX-treated groups and the normal control group. Heart functions of the animals were detected by echocardiography. Quantitative real-time PCR was used to determine the expression of cardiac remodeling, apoptosis-related genes and mature micoRNAs of interest. Results The echocardiography detection showed that cardiac remodeling and impaired heart function were observed after 4-week and 8-week Dox treatment, and the cardiac remodeling and decreased ejection fraction （EF%） and fractional shortening （FS%） were efficiently rescued in the corresponding 4-week and 8-week Dox plus DEX-treated groups. The myocardial expression of Anp and CTGF mRNA was significantly upregulated by Dox treatment, but the upregulation of Anp and CTGF mHNA was blocked in the Dox plus DEX-treated groups. IGF-1 mRNA was significantly up-regulated in rat myocardium in Dox plus DEX-treated groups, with no significant changes of Bcl-2 and BAX mRNA expression. Mature miRNAs determination demonstrated that the myocardial miR-1 and -30e were significantly down-regulated and miR-21 and -208b were significantly up-regulated in Dox treatment groups, but the above miRNA dysregulation could be efficiently reversed after DEX treatment. Conclusions DEX could tune the microRNAs dysregulation inBackground The co-administration of dexrazoxane （DEX） with each dose of doxoruhicin （Dox） is an efficient strategy to relieve Dox-induced cardiotoxicity, however, the mechanisms underlying the cardioprotective effect of DEX have not been well elucidated. MieroRNAs （miRNAs） are endogenous, small non-coding RNAs that negatively regulate gene expression in diverse biological and pathological processes. The aim of the present study was to investigate whether the certain cardiac miRNAs were involved in DOX-induced cardiotoxicity. Methods Male SD rats were randomized into five groups, including the 4-week （cumulative dose： 16 mg/kg） and the 8-week （cumulative dose： 32 mg/kg） Dox-treated groups, and the corresponding 4-week and 8-week Dox plus DEX-treated groups and the normal control group. Heart functions of the animals were detected by echocardiography. Quantitative real-time PCR was used to determine the expression of cardiac remodeling, apoptosis-related genes and mature micoRNAs of interest. Results The echocardiography detection showed that cardiac remodeling and impaired heart function were observed after 4-week and 8-week Dox treatment, and the cardiac remodeling and decreased ejection fraction （EF%） and fractional shortening （FS%） were efficiently rescued in the corresponding 4-week and 8-week Dox plus DEX-treated groups. The myocardial expression of Anp and CTGF mRNA was significantly upregulated by Dox treatment, but the upregulation of Anp and CTGF mHNA was blocked in the Dox plus DEX-treated groups. IGF-1 mRNA was significantly up-regulated in rat myocardium in Dox plus DEX-treated groups, with no significant changes of Bcl-2 and BAX mRNA expression. Mature miRNAs determination demonstrated that the myocardial miR-1 and -30e were significantly down-regulated and miR-21 and -208b were significantly up-regulated in Dox treatment groups, but the above miRNA dysregulation could be efficiently reversed after DEX treatment. Conclusions DEX could tune the microRNAs dysregulation in

关 键 词：CARDIOTOXICITY DOXORUBICIN DEXRAZOXANE APOPTOSIS cardiac remodeling MICRORNAS 

分 类 号：R541[医药卫生—心血管疾病]