Pharmacological postconditioning with tanshinone IIA attenuates myocardial ischemia-reperfusion injury in rats by activating the phosphatidylinositol 3-kinase pathway.

Xun Yuan,Lianglong Chen,Songbo Jing,Lingzhen Wu,Jun Fang

doi:10.3892/etm.2014.1820

Xun Yuan, Lianglong Chen + Show 3 more

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https://doi.org/10.3892/etm.2014.1820

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Abstract

Tanshinone IIA, one of the active ingredients in the Chinese medicine Danshen, is cardioprotective when applied prior to sustained myocardial ischemia. The present study aimed to investigate whether pharmacological postconditioning with tanshinone IIA attenuates myocardial ischemia-reperfusion injury when applied prior to prolonged reperfusion following a sustained ischemia. A total of 88 Sprague-Dawley rats received 30 min myocardial ischemia followed by 5 or 120 min reperfusion. Compared with the ischemia-reperfusion model group, the group that received an intravenous injection of 10 mg/kg tanshinone IIA prior to reperfusion had a reduced myocardial infarct size, higher levels of phospho-Akt and phospho-endothelial nitric oxide synthase and less reduction in the optical density of the mitochondria at 540 nm, indicating that the mitochondrial permeability transition (MPT) was attenuated. The cardioprotective effect conferred by tanshinone IIA was abolished by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). These results demonstrate that tanshinone IIA postconditioning protects the myocardium from ischemia-reperfusion injury through the PI3K/Akt pathway, and the MPT may be also involved in this process.

Highlights

Reperfusion, as the most important technique for salvaging ischemic myocardium, may lead to detrimental myocardial ischemia‐reperfusion injury (MIRI) [1]
It was demonstrated that pharmacological postconditioning with tanshinone IIA, one of the active ingredients in the Chinese medicine Danshen, protects the myocardium from ischemia‐reperfusion injury by activating the phosphatidylinositol 3‐kinase (PI3K)/Akt‐eNOS pathway, and the blockage of mitochondrial permeability transition pore (mPTP) opening may be involved in this cardioprotective effect
This may be as a result of the marked differences that exist between the clinical setting and studies in animal models

Summary

Introduction

Reperfusion, as the most important technique for salvaging ischemic myocardium, may lead to detrimental myocardial ischemia‐reperfusion injury (MIRI) [1]. Ischemic postconditioning, which is induced by a short series of repetitive cycles of reperfusion and ischemia applied immediately at the onset of prolonged reperfusion, has been reported to be cardioprotective against MIRI. In the clinical setting, ischemic postconditioning may be difficult to introduce, i.e., repetitive inflations and deflations of the balloon during primary angioplasty may lead to coronary endothelial damages, plaque rupture and embolic events. The concept of pharmacological postconditioning by administering bioactive agents, which mimic the protective effects of ischemic postconditioning, deserves more attention for its feasible, effective and safer characteristics [4,5]

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