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辛伐他汀通过氧化应激减轻蒽环类药物心脏毒性的相关性研究

李 凤梅, 郝 长来

摘要

目的 研究辛伐他汀通过氧化应激减轻蒽环类药物心脏毒性。方法 将30只雄性Wistar大鼠随机均分为6组,生理盐水组(N)(0.9%NaCl,1ml/kg/隔日灌胃);辛伐他汀组(T)(3mg/kg/隔日灌胃);右丙亚胺组(Y)(25mg/kg/周尾静脉注射);阿霉素组(D)(2.5mg/kg/周尾静脉注射);阿霉素+辛伐他汀组(DT)(Sim: 3mg/kg/隔日灌胃+Dox:2.5mg/kg/周尾静脉注射,另外提前连续7天给予辛伐他汀进行干预); 阿霉素+辛伐他汀组(DY)(Y:25mg/kg/周尾静脉注射半小时后进行Dox:2.5mg/kg/周尾静脉注射)。连续给药2个月,建立阿霉素诱导的心脏毒性(Doxorubicin induce cardiotoxicity,DIC)大鼠损伤模型。观察大鼠的体质量变化;采用HE染色观察各组大鼠心肌情况;采用Western blot法检测各组大鼠心肌组织中SOD-2蛋白表达情况。结果 体重显示阿霉素导致大鼠体重明显降低(P<0.05)),阿霉素联合辛伐他汀或右丙亚胺中表达增加(P<0.05)。HE染色显示阿霉素导致大鼠心肌纤维结构扭曲,断裂溶解等。阿霉素联合辛伐他汀或右丙亚胺的大鼠明显减轻心肌细胞异常形态。Western blot结果显示SOD-2蛋白在阿霉素大鼠模型中表达降低(P<0.05),在阿霉素联合辛伐他汀或右丙亚胺中表达增加(P<0.05)。结论 辛伐他汀可保护DIC,其机制可能与抑制氧化应激相关,这为探索DIC的新型保护药和新的诊断性生物标志物提供新见解。

关键词

阿霉素;超氧化物歧化酶SOD-2;辛伐他汀

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参考

[1] Sheibani M,Azizi Y,Shayan M,et al. Doxorubicin-Induced Cardiotoxicity:An Overview on Pre-clinical Therapeutic Approaches[J].Cardiovasc Toxicol,2022,22(4):292-310.

[2] Christidi E, Brunham L R. Regulated cell death pathways in doxorubicin-induced cardiotoxicity [J]. Cell Death Dis, 2021,12(4):339.

[3] Kong C Y,Guo Z,Song P,et al.Underlying the Mechanisms of Doxorubicin-Induced Acute Cardiotoxicity:Oxidative Stress and Cell Death[J]. Int J Biol Sci,2022,18(2):760-770.

[4] Chotenimitkhun R,D'agostino R,Jr.,Lawrence J A,et al.Chronic statin administration may attenuate early anthracycline-associated declines in left ventricular ejection function[J].Can J Cardiol, 2015,31(3):302-7.

[5] Sawicki K T,Sala V,Prever L,et al.Preventing and Treating Anthracycline Cardiotoxicity:New Insights[J].Annu Rev Pharmacol Toxicol,2021,61: 309-332.

[6] Wei M F,Cheng C H,Wen S Y,et al. Atorvastatin Attenuates Radiotherapy-Induced Intestinal Damage through Activation of Autophagy and Antioxidant Effects[J].Oxid Med Cell Longev,2022,2022:7957255.

[7] Cappetta D,De Angelis A,Sapio L,et al.Oxidative Stress and Cellular Response to Doxorubicin:A Common Factor in the Complex Milieu of Anthracycline Cardiotoxicity[J].Oxid Med Cell Longev,2017,2017:1521020.

[8] Patel R,Nagueh S F,Tsybouleva N,et al.Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy[J].Circulation,2001, 104(3):317-24.

[9] Kim M J,Bible K L,Regnier M,et al. Simvastatin provides long-term improvement of left ventricular function and prevents cardiac fibrosis in muscular dystrophy[J].Physiol Rep,2019,7(6): e14018.

[10]Bjørnstad R,Reiten I N, Knudsen K S,et al. A liposomal formulation of simvastatin and doxorubicin for improved cardioprotective and anti-cancer effect [J].Int J Pharm,2022,629:122379.


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