天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (1): 46-50.doi: 10.3969/j.issn.0253-9896.2015.01.012

• 实验研究 • 上一篇    下一篇

PI3K-Akt、mito-KATP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

刘春伟 1， 丛洪良 1△， 于雪芳 2， 韩薇 3   

  1. 1 天津市胸科医院心内科（邮编 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
  • 收稿日期:2014-01-06 修回日期:2014-08-27 出版日期:2015-01-15 发布日期:2015-01-30
  • 通讯作者: 丛洪良,通讯作者 E-mail： hongliangcong@163.com E-mail:liuchunwei008@163.com
  • 作者简介:刘春伟（1986）， 男， 硕士研究生， 主要从事心肌缺血再灌注损伤研究

Cardioprotective effects of atorvastatin postconditioning on ischemia-reperfusion injury in isolated rat heart: the role of PI3K-Akt, mito-KATPchannel and mPTP

LIU Chunwei1, CONG Hongliang1△, YU Xuefang2, HAN Wei3   

  1. 1 Department of Cardiology, Tianjin Chest Hospital, Tianjin 300222, China; 2 Department of Cardiology, General Hospital of Tianjin Medical University; 3 Department of Cardiac Surgery, Anzhen Hospital
  • Received:2014-01-06 Revised:2014-08-27 Published:2015-01-15 Online:2015-01-30
  • Contact: △CONG Hongliang,Corresponding Author E-mail： hongliangcong@163.com E-mail:liuchunwei008@163.com

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摘要： 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(mPTP)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 mPTP 开放剂苍术甙（ATR）组（ATV+ATR 组）、ATR 组， 乙醇对照组。 进行 30 min 缺血， 120 min 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 mPTP 开放， 产生心肌保护作用。

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

Abstract: Abstract： Objective To observe the postconditioning cardioprotective effects of atorvastatin (ATV) on ischemia-re⁃ perfusion 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 mi⁃ to-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-pro⁃ tein 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-KATPchannel opening and inhibiting mPTP opening.

Key words: myocardial reperfusion injury, 1-phosphatidylinositol 3-kinase, KATP channels, adenosine triphosphate, mitochondria, cell membrane permeability, atorvastatin postconditioning