阿托伐他汀预处理对大鼠缺血-再灌注心肌氧自由基和凋亡的影响

Effect of atorvastatin pretreatment on myocardium oxygen free radical and apoptosis of the rats with myocardial ischemla - repcrfusion injury

目的观察短期阿托伐他汀预处理对心肌缺血-再灌注损伤（MIRI）大鼠心肌超氧化物歧化酶（SOD）和丙二醛（MDA）浓度、心肌细胞内Caspases-3、Caspases-8和NF—κB表达的影响，探讨阿托伐他汀的心肌保护作用机制。方法将80只雄性SD大鼠随机等分为四组：假手术组（A组，生理盐水5mL／d）、缺血再灌注组（B组，生理盐水5mL／d）、阿托伐他汀标准剂量预处理组（C组，阿托伐他汀20mg／d）和阿托伐他汀强化剂量预处理组（D组，阿托伐他汀40ms／d）。灌胃3d后，第4天制作大鼠在体心肌I／R模型，结扎左冠状动脉前降支30rain，再灌注120rain后，用比色法检测心肌中MDA和SOD浓度，Westernblot检测活化Caspase-3、Caspase-8和NF—κB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），Caspases-3和Caspases-8表达明显减少（P〈0．05），NF—κB表达明显减少（P〈0．05）；与C组比较，D组SOD浓度增加更为明显（P〈0．05），MDA、Caspases-3和Caspases-8及NF—κB表达减少更为明显（P〈O．05）。结论阿托伐他汀预处理明显增强抗氧化酶活性，抑制脂质过氧化损伤，降低细胞凋亡，减轻MIRI损伤，表现出较强的心肌保护作用，其机制可能与增加心肌NF—κB表达有关。

Objective To observe the short - term effect of atorvastatin on myocardial superoxide dismutase （ SOD ）, malondialdehyde （ MDA ） concentration in myocardial cells, and expression of nuclear transcription factor - kappaB （ NF - κB ）, Caspases - 8 and Caspases - 3 in the rats with myocardial ischcmia - reperfusion injury （ MIRI）, and to discuss the myocardial protection mechanism of atorvastatin. Methods 80 male SD rats were randomly divided into 4 groups： sham operation group （ A group, normal saline 5 mL/d）, ischemia - reperfusion group （ B group, normal saline 5 mL/d）, standard dose of atorvastatin pretreatment group （C group, atorvastatin 20 mg/d） and intensive dose of atorvastatin pretreatment group （D group, atorvastatin 40 mg/d）. At 3 d after intragastric administration, the rats were made myocardial I/R models, the left anterior descending coronary artery was ligated for 30 rain and reperfused for 120 rain, colorimetric method was used to detect the concentration of MDA and SOD, and the expression of activated Caspase - 3, Caspase - 8 and NF - κB was determined by Western blot. Results Compared with B group, SOD concentration was increased, MDA concentration was decreased significantly（ P 〈 0. 05）, the expressions of Caspases -3,Caspases - 8 and NF - κB were decreased obviously in C group （ P 〈 0.05 ） ; Compared with C group, SOD concentration was increased more significantly（P 〈 0.05 ）, the expressions of MDA, Caspases -3, Caspases - 8 and NF - κB were decreased 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 myocardial NF - κB content.