阿托伐他汀通过抑制NF-κB对抗大鼠缺血再灌注心肌炎症反应和凋亡的机制

Prevention of atorvastalin from inflammatory reaction and apoptosis through inhibition of NF-κB pathway in rats with myocardial ischemia-reperfusion injury

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)肿瘤坏死因子(TNF)和白细胞介素-l(IL-1)、心肌细胞内Caspases-3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40只雄性SD大鼠随机等分为4组:假手术组(A组,0.9%氯化钠溶液5ml/d),缺血再灌注组(B组,0.9%氯化钠溶液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40mg/d)。灌胃7d后,第8天制作大鼠在体心肌I/R模型,结扎左冠状动脉前降支30min,再灌注120min后,用ELISA法检测心肌中TNF-α和IL-1β水平,Western blot检测活化Caspase-3和NF-κB的表达。结果:与B组比较,C组TNF-α、IL-1β、Caspases-3、NF-κB水平均明显减少(均P<0.05);与C组比较,D组TNF-α、IL-1β、Caspases-3及NF-κB表达减少更为明显(均P<0.05)。结论:阿托伐他汀预处理明显抑制炎症反应,减少细胞凋亡,减轻MIRI损伤,呈现较强的心肌保护作用,其机制可能与抑制心肌NF-κB表达有关。

Objective：To observe effect of atorvastatin on myocardial tumornecrosisfactor（TNF）,interleukin-1（IL-1）concentrations in myocardial cells,and to detected expressions of Caspase-3and nuclear factor-κB（NF-κB）in the rats with myocardial ischemia-reperfusion injury（MIRI）,to discuss the myocardial protection mechanism of atorvastatin.Method：Forty 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 20 mg/d）and intensive dose of atorvastatin pretreatment group（D group,atorvastatin 40mg/d）.After 7days of intragastric administration of atorvastatin,the rats were made myocardial I/R models at 8th,the left anterior descending coronary artery was ligated for 30 min and reperfused for 120 min.ELISA method was used to detect the concentrations of TNF and IL-1,and the expressions of Caspase-3and NF-κB were determined by Western blot.Result：Compared with B group,TNF and IL-1concentrations were decreased obviously（both P〈0.05）.The expressions of Caspases-3and NF-κB were decreased in C group significantly（both P〈0.05）.Compared with C group,TNF and IL-1concentration,Caspase-3and NF-κB expressions were decreased more obviously in D group（all P〈0.05）.Conclusion：Atorvastatin pretreatment significantly inhibits inflammation,decreases the apoptosis and reduces MIRI.It shows a strong protective effect,and its mechanism may be related to inhibition of NF-κB expression in myocardial cells.