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北五味子乙素对大鼠离体心肌缺血再灌注损伤的保护作用及分子机制

孙红霞,陈建光*   

  1. 北华大学药学院,吉林 吉林 132013
  • 出版日期:2016-08-15 发布日期:2016-08-30

Protective Effect of Schisandrin B on the Isolated Rat Heart against Myocardial Ischemia/Reperfusion Injury and Its Molecular Mechanism

SUN Hongxia, CHEN Jianguang*   

  1. Pharmaceutical College, Beihua University, Jilin 132013, China
  • Online:2016-08-15 Published:2016-08-30

摘要:

目的:观察北五味子乙素(schisandrin B,SchB)对缺血再灌注(ischemia/reperfusion,I/R)大鼠离体心脏功能、梗死面积、乳酸脱氢酶及相关蛋白表达的影响,探讨其对I/R损伤的保护作用及分子机制。方法:Wistar大鼠50 只,随机分为5 组:空白对照组(CON)、缺血再灌注组(I/R)、SchB预保护组(SchB)、PI3K抑制剂组(I/R+SchB+LY)、腺苷酸活化的蛋白激酶(AMP-activated protein kinase,AMPK)抑制剂组(I/R+SchB+CC)。采用Langendorff法建立离体大鼠心脏I/R模型,心肌缺血2 h,再灌注5、15、30、60 min。观察I/R期间室内压最大上升速率(+dp/dtmax)、室内压最大下降速率(-dp/dtmax)、左心室舒张末压、冠脉流量和心率;测定心脏灌流液中乳酸脱氢酶(lactate dehydrogenase,LDH)含量,2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltertrazoliumchloride,TTC)染色测定各组心肌梗死面积;免疫印迹检测心肌中总蛋白激酶B(protein kinase B,PKB)、磷酸化Akt(p-Akt)、总糖原合成酶激酶-3β(glycogen synthease kinase-3β,GSK-3β)、磷酸化GSK-3β(p-GSK-3β)蛋白表达。结果:SchB可显著改善I/R所致的心肌功能损伤,减少梗死面积,提高心肌中p-Akt和p-GSK-3β蛋白表达。结论:SchB对大鼠离体心脏I/R损伤具有一定保护作用,其机制可能与激活AMPK和PI3K/Akt信号通路有关。

关键词: 北五味子乙素, 心肌缺血再灌注, 损伤, 分子机制

Abstract:

Objective: To observe the effect of schisandrin B (SchB) on cardiac function, infarct size, lactate dehydrogenase
and related protein expression in the isolated heart from rats with myocardial ischemia/reperfusion (I/R) injury and
consequently to explore its protective effect against I/R injury and the underlying molecular mechanism. Methods:
Fifty Wistar rats were randomly divided into five groups: control group (Control), ischemia/reperfusion group (I/R) and
SchB preconditioning group (SchB), PI3K inhibitor group (I/R + SchB + LY294002), and AMPK inhibitor group (I/R +
SchB + Compound C). The Langendorff method was used to establish the isolated rat heart model of I/R injury, ischemia
for 2 h, reperfusion for 5, 15, 30 and 60 min respectively. The +dp/dtmax, −dp/dtmax, left ventricular end-diastolic pressure
(LVEDP), coronary flow (CF), heart rate (HR) and LDH activity in perfusion fluids were observed during I/R period. The
myocardial infarct area was measured with TTC staining and myocardial total Akt, phosphorylation Akt, total GSK-3β and
phosphorylation GSK-3β protein expression were evaluated by the Western blotting technique. Results: SchB significantly
improved the myocardial damage caused by I/R injury, reduced infarct size, and increased the expression of p-Akt and
p-GSK-3β. Conclusion: SchB has protective effects against I/R damage in isolated hearts from rats, which may be related to
the activation of the AMPK and PI3K/Akt signaling pathways.

Key words: schisandrin B, myocardial ischemia/reperfusion, injury, molecular mechanism

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