Electroacupuncture at different frequencies (5Hz and 25Hz) ameliorates cerebral ischemia-reperfusion injury in rats: possible involvement of p38 MAPK-mediated anti-apoptotic signaling pathways

BMC Complementary and Alternative Medicine

Ching-Liang Hsieh¹  Shung-Te Kao²  Nou-Ying Tang²  Jaung-Geng Lin²  Chin-Yi Cheng³ 

[1] Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan;School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan;Department of Chinese Medicine, Hui-Sheng Hospital, Taichung, 42056, Taiwan

关键词: X-linked inhibitor of apoptosis protein;    Bcl-xL;    Bcl-2;    Phospho-p38 MAPK;    Mitogen-activated protein kinases;    Electroacupuncture;   

Others  :  1219992
DOI  :  10.1186/s12906-015-0752-y

 received in 2014-12-28, accepted in 2015-06-29,  发布年份 2015

【 摘 要 】

Background

This study aimed to determine the effects of electroacupuncture stimulation at the Baihui (GV20) and Fengfu (GV16) acupoints, at frequencies of 5Hz (EA-5Hz) and 25Hz (EA-25Hz), 7 days after cerebral ischemia-reperfusion (I/R) injury, and to evaluate the possible signaling mechanisms involved in mitogen-activated protein kinase (MAPK) pathways.

Methods

Rats were subjected to 30 min of middle cerebral artery occlusion (MCAo) followed by 7 days of reperfusion. EA-5Hz or EA-25Hz was applied immediately after MCAo and then once daily for 7 consecutive days.

Results

Results indicated that EA-5Hz and EA-25Hz both markedly attenuated cerebral infarction and neurological deficits. EA-5Hz and EA-25Hz both markedly downregulated cytosolic glial fibrillary acidic protein (GFAP), mitochondrial Bax, mitochondrial and cytosolic second mitochondrial-derived activator of caspase/direct inhibitor of apoptosis protein-binding protein with low isoelectric point (Smac/DIABLO), and cytosolic cleaved caspase-3 expression, and effectively restored cytosolic phospho-p38 MAPK (p-p38 MAPK), cytosolic cAMP response element-binding protein (CREB), mitochondrial Bcl-xL, and cytosolic X-linked inhibitor of apoptosis protein (XIAP) expression, in the ischemic cortical penumbra 7 days after reperfusion. Both EA-5Hz and EA-25Hz also significantly increased the ratios of mitochondrial Bcl-xL/Bax and Bcl-2/Bax, respectively.

Conclusions

Both EA-5Hz and EA-25Hz effectively downregulate reactive astrocytosis to provide neuroprotection against cerebral infarction, most likely by activating the p38 MAPK/CREB signaling pathway. The modulating effects of EA-5Hz and EA-25Hz on Bax-mediated apoptosis are possibly due to the activation of p38 MAPK/CREB/Bcl-xL and p38 MAPK/CREB/Bcl-2 signaling pathways, respectively, and eventually contribute to the prevention of Smac/DIABLO translocation and subsequent restoration of XIAP-mediated suppression of caspase-3 in the cortical periinfarct area 7 days after reperfusion.

【 授权许可】

   
2015 Cheng et al.

【 图 表 】

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