辛伐他汀对阿霉素诱导的心脏毒性大鼠的保护机制研究  

Protective mechanism of simvastatin on cardiotoxicity induced by doxorubicin in rats

作　　者：李凤梅 白春强 郝长来[1] 王丽红[1] LI Feng-mei;BAI Chun-qiang;HAO Chang-lai;WANG Li-hong(Affiliated Hospital of Chengde Medical College,Chengde Hebei 067000)

机构地区：[1]承德医学院附属医院,河北承德067000

出　　处：《中南药学》2024年第11期2919-2925,共7页Central South Pharmacy

基　　金：2018年度河北省医学科学研究重点课题计划(No.20181154)。

摘　　要：目的探讨辛伐他汀对阿霉素诱导的心脏毒性大鼠的保护作用及可能机制。方法将32只Wistar雄性大鼠随机均分为对照组(Con)、辛伐他汀组(Sim)、阿霉素组(Dox)、联合用药组(Dox+Sim)。通过大鼠的一般状态、彩超、ELISA法、HE染色、Masson染色评估辛伐他汀的心脏保护情况;通过Western blot法和qRT-PCR法研究辛伐他汀作用的机制。结果辛伐他汀能够显著降低Dox诱导的心脏毒性,改善心功能;减轻心肌纤维排列紊乱,抑制胶原过度增生;降低纤维化相关因子MMP2、MMP9和CollagenⅠ的表达,增加TIMP1表达;抑制信号通路相关因子TGF-β和Smad2/3的表达。结论辛伐他汀可降低阿霉素相关心脏毒性,其作用机制可能与抑制TGF-β/Smad/MMPs信号通路活性,减少心肌纤维化有关。Objective To determine the protective effect of simvastatin(Sim)on doxorubicininduced cardiotoxicity in rats and its possible mechanism.Methods Totally 32 male Wistar rats were randomly divided into 4 groups:a control group(Con),a simvastatin group(Sim),a doxorubicin group(Dox)and a combination group(Dox+Sim).The general state of rats,color Doppler ultrasound,ELISA,HE staining and Masson staining were used to evaluate the cardiac protection of simvastatin.Western blot and qRT-PCR were used to determine the mechanism of simvastatin.Results Simvastatin greatly reduced Dox-induced cardiac injury and improved cardiac function;alleviated the disorder of myocardial fiber arrangement and inhibited the excessive proliferation of collagen.The expression of MMP-2,MMP-9 and Collagen Ⅰ were decreased,while the expression of TIMP1 was increased.Simvastatin also inhibited the expression of TGF-β and Smad2/3.Conclusion Simvastatin can reduce doxorubicin-related cardiotoxicity,whose mechanism may be related to inhibiting TGF-β/Smad/MMPs signaling pathway and reducing myocardial fibrosis.

关 键 词：辛伐他汀 阿霉素 心肌纤维化 TGF-β/Smad/MMPs信号通路 

分 类 号：R96[医药卫生—药理学]