阿托伐他汀联合吡格列酮对大鼠缺血再灌注心肌的保护作用

Protective Effect of Atorvastatin and Pioglitazone on Ischemia and Reperfusion Myocardium in Rats

目的探讨阿托伐他汀、吡格列酮及二者联用预处理大鼠后,对缺血再灌注(I/R)心肌的保护作用,并探讨其可能的机制。方法选雄性健康Sprague-Dawley(SD)大鼠40只,将上述大鼠随机分为5组:假手术组(生理盐水,2mL/d,8例)I、/R组(生理盐水,2mL/d,8例)、阿托伐他汀组[阿托伐他汀,20mg/(kg.d),8例]、吡格列酮组[吡格列酮,3mg/(kg.d),8例]、阿托伐他汀+吡格列酮组[阿托伐他汀,20mg/(kg.d)+吡格列酮3mg/(kg.d)8,例]。灌胃1周后,第8天制作大鼠在体心肌I/R模型。缺血30min,再灌注1h后测定血清丙二醛(MDA)及超氧化物歧化酶(SOD);Evans blue、TTC双重染色后,用图像分析软件计算梗死面积。结果阿托伐他汀组、吡格列酮组、阿托伐他汀+吡格列酮组与I/R组比较,心肌梗死面积减少,SOD升高、MDA降低(P<0.01)。联合用药组较单独用药组心肌梗死面积减少,SOD升高,MDA降低(P<0.01);较假手术组SOD降低,MDA升高(P<0.01)。阿托伐他汀组与吡格列酮组各指标水平接近(P>0.05)。结论阿托伐他汀、吡格列酮能减轻心肌缺血再灌注损伤,两药联合应用作用更加明显,其作用机制与提高血清SOD活性,降低MDA含量有关。

Objective To investigate atorvastatin,pioglitazone and two drugs in combination on ischemia-reperfusion myocardial pro- tective effects and the possible mechanism. Methods All 40 healthy SD rats were randomly divided into 5 groups：sham operation group （n=8,0.9%sodium chloride injection liquid,2mL/d）,I/R group （n=8,0.9% sodium chloride injection liquid,2mL/d）,atorvastatin group[（n=8, atorvastatin, 20mg/kg· d）], pioglitazone group[n=8, pioglitazone 3mg/（kg ·d）],atorvastatin ＋ pioglitazone group[n=8, atorvastat in, 20mg/（kg·d）＋pioglitazone 3mg/（kg·d）].After one week garage make the rat model of myocardial ischemia-reperfusion in eight days,is chemia 30minute, one hour after reperfusion serum malondialdehyde （MDA） and superoxide dismutase （ SOD ）.Evans blue, Trc double staining,using image analysis software to calculate infarct size. Results The atorvastatin group,pioglitazone group,atorvastatin ＋ pioglita zone group and I/R group,infarct size reduction,SOD increased,MDA decreased（P〈0.01 ）.Atorvastatin ＋ pioglitazone group than in the atorvastatin group,pioglitazone group myocardial infarct size reduction,SOD increased,MDA decreased（P〈0.01 ）.Compared with the sham group SOD decreased,MDA increased（P《0.01 ）. Atorvastatin group and pioglitazone group close to the target level（P〉0.05）. Conclu- sion Atorvastatin, pioglitazone can reduce myocardial ischemia-reperfusion injury,its role in combination of two drugs is more obvious. The mechanism is mediated by increasing SOD activity and decreasing MDA.