辛伐他汀对老年小鼠心肌缺血再灌注时氧化应激及细胞凋亡的影响  

Effects of Simvastatin on Oxidative Stress and Cell Apoptosis in Aged Mice with Myocardial Ischemia-reperfusion

作　　者：廖小龙[1] 王首红[1] 王中华[1] 郭伟新[1] 温剑艺[1] 覃铁和[1] 

机构地区：[1]广东省人民医院/广东省医学科学院广东省老年医学研究所重症医学科,广州510080

出　　处：《中国药房》2016年第19期2626-2629,共4页China Pharmacy

基　　金：广东省人民医院院内博士启动项目(No.2014b003)

摘　　要：目的:研究辛伐他汀对老年小鼠心肌缺血再灌注(IR)时氧化应激及细胞凋亡的影响。方法:取老年小鼠随机分为假手术组(磷酸盐缓冲液)、模型组(磷酸盐缓冲液)和辛伐他汀低、中、高剂量组(2.5、5、20 mg/kg),每组14只。各组小鼠于造模前ip相应药物7 d,每天1次。除假手术组外其余各组小鼠复制IR模型。检测各组小鼠心肌梗死面积比例、心肌细胞凋亡率、心肌组织中凋亡基因Caspase-3活性、Bax和Bcl-2蛋白表达、蛋白激酶B(Akt)磷酸化水平、血清中丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果:与假手术组比较,模型组小鼠心肌梗死面积比例、心肌细胞凋亡率、Caspase-3活性、Bax蛋白表达和MDA含量均增加,Bcl-2蛋白表达、Akt磷酸化水平和SOD活性均降低(P<0.01);与模型组比较,辛伐他汀高剂量组小鼠心肌梗死面积比例、心肌细胞凋亡率、Caspase-3活性、Bax蛋白表达、MDA含量均降低,Bcl-2蛋白表达、Akt磷酸化水平、SOD活性均升高(P<0.01);辛伐他汀低、中剂量组小鼠上述指标差异均无统计学意义(P>0.05)。结论:辛伐他汀能显著减轻老年小鼠心肌IR损伤,其机制可能与抑制心肌细胞凋亡和氧化应激产物生成有关。OBJECTIVE：To study the effects of simvastatin on oxidative stress and cell apoptosis in aged mice with myocardial ischemia-reperfusion（IR）.METHODS：Aged mice were randomly divided into sham operation group（phosphate buffer solution）,model group（phosphate buffer solution）and simvastatin low-dose,medium-dose and high-dose groups（2.5,5 and 20 mg/kg）with 14 mice in each group.Those groups were given relevant medicine intraperitoneally before modeling for 7 d,once a day.IR model was induced in those groups except for sham operation group.The area ratio of myocardial infarction,myocardial cell apoptosis rate,activity of myocardial tissue apoptosis gene Caspase-3,the protein expression of Bax and Bcl-2,Akt phosphorylation,serum concent of MDA and activity of SOD were all detected.RESULTS：Compared with sham operation group,the area ratio of myocardial infarction,myocardial cell apoptosis rate,Caspase-3 activity,the protein expression of Bax and MDA content were all increased in model group,while the protein expression of Bcl-2,Akt phosphorylation and SOD activity were decreased（P〈0.01）.Compared with model group,the area ratio of myocardial infarction,myocardial apoptosis rate,Caspase-3 activity,the protein expression of Bax and MDA content were all decreased in simvastatin high-dose group,while the protein expression of Bcl-2,Akt phosphorylation and SOD activity were increased（P〈0.01）.There was no statistical significance in above indexes in simvastatin low-dose and medium-dose groups（P〈0.05）.CONCLUSIONS：Simvastatin can relieve myocardial IR injury in aged mice,and the mechanism of which may be associated with inhibiting myocardial cell apoptosis and the generation of oxidative stress.

关 键 词：辛伐他汀 心肌缺血再灌注 氧化应激 心肌细胞凋亡 老年小鼠 

分 类 号：R965[医药卫生—药理学] R972[医药卫生—药学]