Electro-acupuncture at points of Zusanli and Quchi exerts anti-apoptotic effect through the modulation of PI3K/Akt signaling pathway

Abstract

We evaluated the neuroprotective effect of electro-acupuncture (EA) on cerebral ischemia-reperfusion (IR) injury and deeply investigated the relationship between this neuroprotective effect and PI3K/Akt pathway. Rats underwent focal cerebral IR injured by suture method and received the in vivo therapeutic efficacy of EA at points of Zusanli(ST36) and Quchi(LI11) after the operation. We found that the EA treatment significantly (p<0.05) improved neurological deficit and cerebral infarction. Furthermore, EA profoundly activated PI3K/Akt signaling resulted in the inhibition of cerebral cell apoptosis in the ischemic penumbra. Simultaneously EA increased the expression of PI3K, p-Akt, p-Bad and Bcl-2 at the protein level and the expression of Bcl-2 at the mRNA level. On the contrary, EA inhibited the Bax and cleaved Caspase-3-positive expression. The selective PI3K inhibitor LY294002 compromised EA-induced neuroprotective effects and reduced the elevation of p-Akt, p-Bad and Bcl-2 levels. Our data suggested that the PI3K/Akt pathway played a critical role in mediating the neuroprotective effects of EA treatment at points of Zusanli and Quchi after the ischemic stroke.

Keywords: 2,3,5-triphenyl tetra-zolium chloride; 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one; Apoptosis; Cerebral ischemia-reperfusion; DMSO; EA; Electro-acupuncture; IR; LY294002; MCAO; Neuroprutective effect; PBS; PI3K/Akt; PVDF; TTC; TUNEL; dimethylsulfoxide; electro-acupuncture; ischemia/reperfusion; middle cerebral artery occlusion; phosphate buffered saline; phosphoinositide 3-kinase/protein kinase B; polyvinylidene difluoride; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.