Electroacupuncture at different frequencies (5Hz and 25Hz) ameliorates cerebral ischemia-reperfusion injury in rats: possible involvement of p38 MAPK-mediated anti-apoptotic signaling pathways.
Electroacupuncture at different frequencies (5Hz and 25Hz) ameliorates cerebral ischemia-reperfusion injury in rats: possible involvement of p38 MAPK-mediated anti-apoptotic signaling pathways.
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DOI：
10.1186/s12906-015-0752-y
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发表时间：
2015-07-18
影响因子：
--
通讯作者：
Hsieh CL
中科院分区：
文献类型：
--
作者：
Cheng CY;Lin JG;Tang NY;Kao ST;Hsieh CL
本研究旨在观察5 Hz和25 Hz电针刺激百会、风府穴对脑缺血-再灌注损伤（I/R）后7天的影响，并探讨丝裂原活化蛋白激酶（MAPK）信号通路的可能机制。大鼠进行30分钟的大脑中动脉闭塞（MCAo），然后再灌注7天。MCAo后立即电针5 Hz或25 Hz，以后每天1次，连续7天。结果表明，电针5 Hz和25 Hz均能明显减轻脑梗塞和神经功能缺损。电针5 Hz和电针25 Hz均能显著下调细胞浆胶质细胞酸性蛋白（GFAP）、线粒体Bax、线粒体和细胞浆低等电点的caspase活化蛋白/凋亡直接抑制蛋白结合蛋白（Smac/DIABLO），胞浆切割caspase-3表达，并有效地恢复胞浆磷酸化p38 MAPK（p-p38 MAPK）、胞浆cAMP反应元件结合蛋白（CREB）、线粒体Bcl-xL和胞浆X连锁凋亡抑制蛋白（XIAP）表达。电针5 Hz和25 Hz还分别显著增加线粒体Bcl-xL/Bax和Bcl-2/Bax比值。EA-5 Hz和EA-25 Hz都有效地下调反应性星形胶质细胞增多，以提供针对脑梗死的神经保护，这很可能是通过激活p38 MAPK/CREB信号通路。电针5 Hz和25 Hz可能分别通过激活p38 MAPK/CREB/Bcl-xL和p38 MAPK/CREB/Bcl-2信号通路，抑制再灌注7 d后梗死周边区Smac/DIABLO易位，恢复XIAP介导的caspase-3抑制作用，从而抑制凋亡。
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. 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 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. 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.