Objective To explore the effect of aerobic exercise on cognitive function in schizophrenia(SCZ)rats and analyze its mechanism.Methods Sixty-two SPF SD male rats(200～220 g)at seven to eight weeks were in-jected intraperitoneally with dizocilpine maleate(MK-801)for 14 days to establish the SCZ model.According to the random number table method,60 SD rats were divided into model group,aerobic exercise group(rats were trained on the moderate intensity treadmill at a fixed time every day for 20 minutes,with a rest of one day a week for six weeks),aerobic exercise+ATRA group(aerobic exercise+pathway inhibitor-all-trans retinoic acid,40 mg/kg).There were 20 rats in each group and another 20 rats(control group)treated with the same way as the model group,besides in-jecting intraperitoneally with 0.9％sodium chloride injection.Plasma biochemical levels and inflammatory factors were compared among all groups.The injury and apoptosis of hippocampal neurons and pathological changes of small intestine were detected in each group.Intestinal barrier injury and changes of intestinal mucosal permeability and blood-brain barrier permeability were evaluated in each group.The expression of related proteins was detected by Western blot.Results Compared with the control group,the cognitive function of the model group rats decreased,with significant atrophy and inflammatory infiltration of the small intestine villi.The damage and permeability of the intestinal barrier increased,and the permeability of the blood-brain barrier changed.The number of intestinal micro-biota translocation increased,and the hippocampal tissue nerve damage and apoptosis were severe.The levels of plas-ma lipopolysaccharide(LPS),serum neurotransmitters,and inflammatory factors increased,as well as the expression of nuclear transcription factor related factor 2(Nrf2)/antioxidant response element(ARE)/heme oxygenase-1(HO-1)pathway proteins and their mediated antioxidant and anti-inflammatory proteins increased(all P＜0.05).Compared with the model group,the aerobic exercise group showed reduced cognitive function and alleviated intestinal mucosal damage,intestinal barrier damage and permeability changes,blood-brain barrier permeability changes,reduced hip-pocampal tissue nerve damage and apoptosis,decreased levels of plasma LPS,serum neurotransmitters and inflamma-tory factors,and increased expression of Nrf2/ARE/HO-1 pathway proteins and their mediated antioxidant and anti-in-flammatory proteins(all P＜0.05).Compared with the aerobic exercise group,the levels of inflammatory water and oxidative stress in the aerobic exercise+ATRA rats were increased,the cognitive function of the rats was decreased and the intestinal mucosal damage was increased.Conclusions Aerobic exercise may improve cognitive dysfunction by activating Nrf2/ARE/HO-1 anti-inflammatory and antioxidant stress pathways,playing a protective role in gut-brain axis tissue.
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