Mechanism of electroacupuncture in alleviating learning and memory impairment in rats with post-stroke cognitive impairment by regulating the IRS-1/PI3K/AKT signaling pathway and glucose transporters

ObjectiveTo observe the effect of electroacupuncture （EA） on the insulin receptor substrate （IRS）-1/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway and glucose transporters （GLUTs） in the hippocampus of rats with learning and memory impairment after cerebral ischemia-reperfusion injury， so as to explore the mechanism of EA in improving learning and memory impairment in rats with post-stroke cognitive impairment.MethodsFifteen rats were randomly selected from 100 male Sprague-Dawley （SD） rats as the sham operation group， and the remaining 85 rats were subjected to middle cerebral artery occlusion/reperfusion （MCAO/R） modeling using the suture method. Successfully modeled rats were divided into the model， EA， inhibitor， EA+inhibitor， and donepezil groups， with 15 rats in each group， in which， rats in the inhibitor group and EA+inhibitor group were given an intracerebroventricular injection of the pathway inhibitor LY294002 （10 mmol/L， 10 μL） into the left lateral ventricle 30 min before modeling. Rats in the EA group and EA+inhibitor group received EA intervention at “Shenting” （GV24） and “Baihui” （GV20） acupoints， 30 min per session， once a day. Rats in the donepezil group were given donepezil by gavage at a dose of 0.92 mg·kg-1·d-1， once a day. Rats in the treatment group were given continuous intervention for 14 d. Zea-Longa scoring and novel object recognition test were used to evaluate neurological damage and learning and memory ability； TTC staining was used to assess cerebral infarct volume； HE staining was used to observe the pathological morphology changes of hippocampal tissue in the infarcted area； a glucose detection kit was used to measure hippocampal glucose content； qPCR was used to detect the mRNA expressions of IRS-1， PI3K， and AKT in the hippocampus； Western blot was used to detect the protein expressions of IRS-1， PI3K， phosphorylated （p）- PI3K， AKT， p-AKT， GLUT1， and GLUT3 in the hippocampus.ResultsCompared with the sham operation group， the model group showed sparse hippocampal cells with pyknosis and hyperchromatism， increased neurological deficit score， cerebral infarct volume， and recognition index to novel objects （PPPPPPPPConclusionEA at GV24 and GV20 may improve the learning and memory function of MCAO/R rats by activating the IRS-1/PI3K/AKT signaling pathway to inhibit insulin resistance and enhance the glucose transport capacity of neurons.