Myocardial post-conditioning with Danshen-Gegen decoction protects against isoproterenol-induced myocardial injury via a PKCε/mKATP-mediated pathway in rats

Sze Man Wong,Limin Zhou,Po Yee Chiu,Kam Ming Ko,Philip Y Lam,Hoi Yan Leung,Zhong Zuo

doi:10.1186/1749-8546-6-7

Abstract

BackgroundDanshen-Gegen decoction (DG), a Chinese herbal formula, has been demonstrated to be effective for the treatment of coronary heart disease such as myocardial infarction. In the present study, we investigated the effect of DG post-conditioning on isoproterenol (ISO)-induced myocardial injury in rats.MethodsISO was injected intraperitoneally (200 mg/kg) to induce acute (2-6 hours) myocardial injury in adult female rats. DG (4 g/kg) was administered per oral immediately after the injection of ISO in the rats. Extent of myocardial injury was assessed by measurements of plasma enzyme activities. Myocardial mitochondrial glutathione antioxidant status, lipid peroxidation and mitochondrial calcium ion loading and cytochrome c release were also measured. Effects of inhibitors of protein kinase C-epsilon (PKCε) ranslocation and mitochondrial ATP-sensitive potassium channel (mKATP) on myocardial post-conditioning by DG were investigated.ResultsISO inflicted acute myocardial injury in the rats as evidenced by increased plasma enzyme activities. DG post-treatment alleviated the ISO-induced acute myocardial injury.ConclusionDG post-treatment protected the myocardium against ISO-induced acute injury in rats. The myocardial post-conditioning by DG is likely mediated by PKCε/mKATP signaling pathway.

Highlights

Danshen-Gegen decoction (DG), a Chinese herbal formula, has been demonstrated to be effective for the treatment of coronary heart disease such as myocardial infarction
The cardioprotection by ischemic post-conditioning is likely linked to the activation of an adenosine-mediated reperfusion-injury salvage kinase (RISK) pathway [10] and a tumor necrosis factor-a-mediated survivor activating factor enhancement (SAFE) pathway [11]; both signaling pathways may target mitochondria via the activation of protein kinase C-epsilon (PKCε), thereby opening a mitochondrial ATP-dependent potassium channel, leading to inhibition of a mitochondrial permeability transition and cardioprotection [12,13,14,15,16]
From the time-dependent changes in plasma enzyme activities as quantified by the area under the curve (AUC), we found that DG post-treatment protected against the ISO-induced increases in plasma enzyme activities by 32% (LDH; P = 0.033), 21% (AST; P < 0.001) and 19% (CPK; P = 0.046) (Figure 1b)

Summary

Introduction

Danshen-Gegen decoction (DG), a Chinese herbal formula, has been demonstrated to be effective for the treatment of coronary heart disease such as myocardial infarction. We investigated the effect of DG post-conditioning on isoproterenol (ISO)-induced myocardial injury in rats. Our recent ex vivo study demonstrated that an aqueous extract of DG preconditioned myocardium against ischemia/reperfusion injury in rats [9]. The cardioprotection by ischemic post-conditioning is likely linked to the activation of an adenosine-mediated reperfusion-injury salvage kinase (RISK) pathway [10] and a tumor necrosis factor-a-mediated survivor activating factor enhancement (SAFE) pathway [11]; both signaling pathways may target mitochondria via the activation of protein kinase C-epsilon (PKCε), thereby opening a mitochondrial ATP-dependent potassium channel (mKATP), leading to inhibition of a mitochondrial permeability transition and cardioprotection [12,13,14,15,16]

Methods

Results

Discussion

Conclusion