阿托伐他汀通过激活Nrf2通路对抗大鼠缺血再灌注心肌氧化应激损伤和凋亡

Prevention of atorvastalin against myocardium oxidative stress and apoptosis of the rats with myocardial ischemia-reperfusion injury through activation of Nrf2 pathway

目的:观察阿托伐他汀预处理对大鼠心肌缺血-再灌注损伤(MIRI)超氧化物歧化酶(SOD)和丙二醛(MDA)浓度、心肌细胞内Caspase-3和Nrf2表达的影响,探讨阿托伐他汀的心肌保护作用机制。方法:将40只雄性SD大鼠随机等分为4组:假手术组(A组)、缺血再灌注组(B组)、阿托伐他汀标准剂量预处理组(C组)和阿托伐他汀强化剂量预处理组(D组)。灌胃7d后,第8天制作大鼠在体心肌MIRI模型,结扎左冠状动脉前降支30min,再灌注120min后,用比色法检测心肌中MDA和SOD浓度,Western blot检测活化Caspase-3和Nrf2的表达。结果:与B组比较,C组SOD浓度明显增加(P<0.05),MDA浓度明显减少(P<0.05),Caspase-3表达明显减少(P<0.05),Nrf2表达明显增多(P<0.05);与C组比较,D组SOD浓度、Nrf2表达增加更为明显(P<0.05),MDA、Caspase-3表达减少更为明显(P<0.05)。结论:阿托伐他汀预处理明显增强抗氧化酶活性,抑制指质过氧化,减少细胞凋亡,减轻MIRI损伤,且呈剂量依赖性,表现较强的心肌保护作用,其机制可能与增加心肌Nrf2表达有关。

Objective：To observe effect of atorvastatin on myocardial superoxide dismutase（SOD）,malondialdehyde（MDA）concentration in myocardial cells,and expression of NF-E2-related factor 2（Nrf2）and Caspase-3in the rats with myocardial ischemia-reperfusion injury（MIRI）,and to discuss the myocardial protection mechanism of atorvastatin.Method：The 40 male SD rats were randomly divided into 4groups：sham operation group（A group,normal saline 5ml/d）,ischemia-reperfusion group（B group,normal saline 5ml/d）,standard dose of atorvastatin pretreatment group（C group,atorvastatin 20mg/d）and intensive dose of atorvastatin pretreatment group（D group,atorvastatin 40mg/d）.At 7dafter intragastric administration,the rats were made myocardial I/R models,and the left anterior descending coronary artery was ligated for 30 min and reperfused for 120 min.Colorimetric method was used to detect the concentration of MDA and SOD,and the expression of Caspase-3and activated Nrf2 was determined by Western blot.Result：Compared with B group,SOD concentration was increased,MDA concentration was decreased obviously（P〈0.05）,the expressions of caspases-3was decreased and Nrf2 was increased in C group significantly（P〈0.05）;Compared with C group,SOD concentration was increased more obviously（P〈0.05）,the concentration of MDA,expressions of caspase-3and Nrf2 were decreased more significantly in D group（P〈0.05）.Conclusion：Atorvastatin pretreatment significantly increases antioxidant enzyme activity,inhibits lipid peroxidation injury,decreases the apoptosis and reduces the myocardial MIRI.It shows a strong protective effect,and its mechanism may be related to increased Nrf2 in myocardial cells.