Objective To evaluate the role of nuclear factor erythroid 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in the improvement in postoperative cognitive function by electroacupuncture pre-conditioning in aged rats.Methods Eighty clean-grade healthy male Sprague-Dawley rats,aged 24 months,weighing 550-600 g,were divided into 4 groups(n=20 each)using a random number table meth-od:control group(C group),POCD group,electroacupuncture+POCD group(EA group),and Nrf2 inhib-itor ML385+electroacupuncture+POCD group(I group).A rat POCD model was prepared by performing ex-ploratory laparotomy under 3％sevoflurane anesthesia.Nrf2 inhibitor ML385 15 mg/kg was intraperitoneally injected at 30 min before surgery in group Ⅰ,while the equal volume of normal saline was given instead in the remaining groups.Electroacupuncture stimulation of the Zusanli,Hegu and Neiguan acupoints(dis-perse-dense waves,current intensity 1 mA,frequency 2/15 Hz,30 min)was performed at 8:00 a.m.every day for 5 days prior to model preparation in EA group and I group.An open field test was conducted at 3 days after operation to measure the autonomous motor function,and Morris water maze test was conducted af-ter the end of the open field test at 3-7 days after operation to evaluate the cognitive function.After the Mor-ris water maze test,the rats were sacrificed under anesthesia and hippocampal tissues were taken for deter-mination of the level of reactive oxygen species(ROS,by flow cytometry)and expression of Nrf2 and HO-1(by Western blot)and for examination of the mitochondrial ultrastructure of hippocampal neurons(with a transmission electron microscope).Results Compared with group C,the escape latency was significantly prolonged,the number of crossing the original platform quadrant was decreased,the hippocampal ROS lev-els were increased,the expression of Nrf2 and HO-1 was down-regulated(P＜0.05),and mitochondria were swollen and mitochondrial cristae were broken in the hippocampal CA1 neurons in group POCD.Compared with group POCD,the escape latency was significantly shortened,the number of crossing the original plat-form quadrant was increased,the hippocampal ROS levels were decreased,the expression of Nrf2 and HO-1 was up-regulated(P＜0.05),and the swelling of mitochondria and rupture of cristae structure were improved in the hippocampal CA1 neurons in group EA.Compared with group EA,the escape latency was significant-ly prolonged,the number of crossing the original platform quadrant was decreased,the hippocampal ROS levels were increased,the expression of Nrf2 and HO-1 was down-regulated(P＜0.05),and the swelling of mitochondria and rupture of cristae structure were aggravated in the hippocampal CA1 neurons in group Ⅰ.Conclusions Activation of the hippocampal Nrf2/HO-1 signaling pathway is involved in improvement in postoperative cognitive function by electroacupuncture preconditioning in aged rats.
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