Shengmai injection attenuates ischemia-reperfusion-induced autophagy correlating to modulating AMPK, mTOR and JNK pathways

Aim Shengmai injection （SMI） , a Chinese patent medicine deprived from an ancient Chinese herbal compound Shengmai san, which is used extensively for the treatment of cardiovascular and cerebrovascular disease in clinic. To determine the neuroprotective effect of SMI, the effect and the relevant mechanism of SMI had been inves- tigated on cerebral ischemia-reperfusion injury in mice. Methods Right middle cerebral artery was occluded by in- serting a thread through intemal carotid artery for 1 h, and then reperfusion for 24 h in mice. Neuroprotective effect was testified using transmission electron microscopic examination, evaluation of infarct volume and neurological defi- cits. Related mechanism was evaluated by western blotting. The SMI was injected intraperitoneally after ischemia for 1 h at doses of 1.42, 2. 84 and 5.68 g · kg^-1. The control group received saline as vehicle of SMI. Results SMI （ 1.42, 2. 84 and 5. 68 g · kg^-1） could significantly reduced the infarct volume, SMI （5.68 g · kg^-1） could signifi- cantly improved the neurological deficits, as well as the neuron＇s morphology change. SMI （5.68 g · kg^-1） could significantly inhibited the autophagy-related proteins： Beclinl and LC3. SMI （5. 68 g · kg^-1） remarkably inhibited the phosphorylation of adenosine monophosphate activated protein kinase （AMPK）, and down-regulated the phospho- rylation of mammalian target of rapamycin （roTOR） and Jun N-terminal kinase （JNK） after 24 h reperfusion. Con-clusion The results indicated that SMI elicits potent protection against cerebral ischemia/reperfusion injury, which may partly be due to the inhibition in autophagy and related signal pathways.