PI3K-Akt、mito-K_(ATP)通道及mPTP在阿托伐他汀后处理减轻大鼠心肌缺血再灌注损伤中的作用  

Cardioprotective effects of atorvastatin postconditioning on ischemia-reperfusion injury in isolated rat heart: the role of PI3K-Akt, mito-K_(ATP) channel and mPTP

作　　者：刘春伟[1] 丛洪良[1] 于雪芳[2] 韩薇[3] 

机构地区：[1]天津市胸科医院心内科,300222 [2]天津医科大学总医院心内科 [3]首都医科大学附属北京安贞医院心外科

出　　处：《天津医药》2015年第1期46-50,共5页Tianjin Medical Journal

摘　　要：目的观察阿托伐他汀(ATV)后处理对离体大鼠心肌缺血再灌注损伤的保护作用,探讨磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)、线粒体ATP敏感性钾通道(mito-KATP通道)及线粒体膜通透性转换孔(m PTP)在其中的作用。方法将雄性Wistar大鼠随机分为对照组(I/R组)、阿托伐他汀后处理组(ATV组)、ATV复合PI3K抑制剂LY294002组(ATV+LY294002组)、LY294002组、ATV复合mito-KATP通道抑制剂5-羟葵酸(5-HD)组(ATV+5-HD组)、5-HD组、ATV复合m PTP开放剂苍术甙(ATR)组(ATV+ATR组)、ATR组,乙醇对照组。进行30 min缺血,120min再灌注。观察各组心肌梗死范围,血流动力学指标,肌酸磷酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)含量,烟酰胺腺嘌呤二核苷酸(NAD+)含量,心肌Akt和磷酸化Akt表达水平。结果 ATV组心肌梗死范围、LDH、CK-MB较I/R组下降(P<0.05),心肌NAD+含量较I/R组增加(P<0.05);ATV+LY294002组、ATV+5-HD组,ATV+ATR组心肌梗死范围、CK-MB、LDH,NAD+较I/R组差异无统计学意义。ATV组较I/R组血流动力学指标改善。Western blot显示ATV组、ATV+5-HD组和ATV+ATR组磷酸化Akt表达较I/R组增加,ATV+LY-294002组、LY-294002组、ATR组、5-HD组磷酸化Akt表达与I/R组相比无增加。结论阿托伐他汀后处理通过激活PI3K-Akt、促进mito-KATP通道开放,抑制m PTP开放,产生心肌保护作用。Objective To observe the postconditioning cardioprotective effects of atorvastatin （ATV） on ischemia-reperfusion injury in isolated rat heart, and the role of phosphatidylinositol-3-kinase , protein kinase B（PI3K-Akt）, mitochon？drial ATP-sensitive potassium （mito-KATP channel） and mitochondrial permeability transition pore （mPTP） thereof. Meth？ods Healthy male Wistar rats were randomly divided into 9 groups：ischemia reperfusion （I/R） control group, atorvastatin postconditioning （ATV） group, ATV plus PI3K inhibitor LY294002 （ATV＋LY294002） group, LY294002 group, ATV plus mito-KATP channel inhibitor 5-hydroxydecanoate （ATV＋5-HD） group, 5-HD group, ATV plus mPTP inhibitor ATR （ATV＋ATR） group, ATR group and ethanol group. Model rats were given 30-min ischemia followed by 120-min reperfusion. The myocardial infarction size, hemodynamic parameters, creatine kinase isoenzyme （CK-MB）, lactate dehydrogenase （LDH）, nic？otinamide adenine dinucleotide （NAD＋） and the expression of myocardial protein kinase B （Akt） and myocardial phospho-protein kinase B （p-Akt） were evaluated. Results Compared with the control group, atorvastatin reduced the myocardial in？farction size, CK-MB and LDH（P〈0.05）, increased NAD＋（P〈0.05）. There were no significant differences in the myocardi？al infarction size, CK-MB, LDH and NAD＋between ATV＋LY294002 group, ATV＋5-HD group and ATV＋ATR group. The hemodynamic parameters were improved in ATV group compared with those in control group. Western blot analysis con？ firmed the significant phosphorylation of Akt in ATV group, ATV＋5-HD group and ATV＋ATR group compared with those of control group. There were no significant differences in the phosphorylation of Akt between ATV ＋LY294002 group, LY294002 group, ATR group and 5-HD group. Conclusion Atorvastatin postconditioning could attenuate the ischemia-re？perfusion injury through activating the PI3K-Akt, promoting mito-KATP channel opening and inhibiting

关 键 词：心肌再灌注损伤 1-磷脂酰肌醇3-激酶 KATP通道 腺苷三磷酸 线粒体 细胞膜通透性 阿托伐他汀后处理 

分 类 号：R654.2[医药卫生—外科学]