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.
出处
《中国药房》
CAS
北大核心
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)
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
Simvastatin
Myocardial ischemia-reperfusion
Oxidative stress
Myocardial cell apoptosis
Aged mice
