| Objective The study was designed to observe the effects of atmospheric PM2.5.5 exposure on cognitive function of offspring rats fed with high-fat diet,and explore the role of Nrf2signaling pathway in cognitive function damage casued by the PM2.5 exposure in offspring rats fed with high-fat diet.The study will provide scientific basis to reveal the mechanisms of cognitive function impairment induced by PM2.5 and high-fat diet.Methods Healthy adult SPF SD rats mated according to male and female ratio of 2:1.Pregnant rats were randomLy divided into six groups,including the control group?CC group,normal diet?,high fat diet group?HFD group?,low PM2.5 group(L-PM2.5 group,normal diet),high PM2.5 group(H-PM2.5 group,normal diet),high fat diet+low PM2.5group(HFD+L-PM2.5 group)and high fat diet+high PM2.5 group(HFD+H-PM2.5 group).The low and high PM2.5.5 exposure concentrations in exposure cabinet were about two times and four times higher than the PM2.5.5 concentration outdoors.The PM2.5-exposed rats were exposed to concentrated PM2.5 coming from outdoor air from pregnant 0 day,5 hours every day,5 days every week,until postnatal day 21?PND21?of offspring.After weaning,the offspring rats continued to be exposed to PM2.5 until PND42,PND60.The rats and their newborn pups in the CC and HFD group were kept in clean room,as well as the PM2.5-exposed rats and offspring after daily PM2.5.5 exposure.After weaning,the offspring rats in all groups were given normal diet.The time of pinna detachment,body hair,incisor eruption and eye opening of the pups were observed,and body weithts were measured regularly.The cognitive function of pups was tested using open field and Morris water maze at PND21,PND42 and PND60.The SOD activity and MDA content in serum and hippocampus of pups at each stage were detected.The mRNA expression levels of Nrf2,HO-1 and NQO1 in hippocampus were determined by RT-qPCR.The protein expression levels of total protein Nrf2,HO-1,NQO1 and nuclear protein Nrf2.in hippocampus were determined by Western-blot.Results 1 The clean room,outdoor,low and high PM2.5 concentrations during the exposure period were?3.52±1.73?,?60.47±21.01?,?127.38±43.16?and?256.45±81.34??g/m3,respectively.2 PM2.5.5 exposure prolonged the eye opening time of newborns,and HFD prolonged the body hair growth time of newborns?P<0.05?.Compared with CC group,the body weight of PND14,PND21 male and female pups in L-PM2.5 group,H-PM2.5 group decreased,while in HFD+L-PM2.5 group increased?P<0.05?.3 In orientation navigation test,compared with CC group,the escape latency of PND42 male pups in HFD+H-PM2.5 group increased on the fourth day of training.Compared with CC group and HFD group,the escape latency of PND60 male pups in HFD+H-PM2.5 group increased on the fourth day of training.In spatial probe test,PM2.5 reduced the traversing platforms number of PND21 male pups and the target quadrant time of PND60 male pups.HFD reduced the target quadrant time of PND42 male pups?P<0.05?.In open field test,HFD shortened the total distance of PND21 male and female pups.PM2.5 and HFD decreased the central area residence time of PND21 male pups.HFD decreased the central area entry times of PND42 male pups?P<0.05?.4 Histopathological changes:The cells in the hippocampus were disordered,the surrounding space was obviously enlarged,the coloration was shallow,the morphology was changed,most of the nucleus was pyknosis and vacuoles changed in PND21,PND42,PND60 pups in HFD+L-PM2.5 and HFD+H-PM2.5 groups.5 PM2.5 reduced SOD activity in hippocampus of PND21 and PND60 male pups.HFD reduced SOD activity in hippocampus of PND21 male pups?P<0.05?.6 There was a synergy effect between PM2.5 and HFD on NQO1 mRNA expression level in hippocampus of PND42 female pups.Compared with CC and L-PM2.5 group,the NQO1mRNA expression level increased in hippocampus of male rats in H-PM2.5 group?P<0.05?.7 PM2.5 and HFD had synergy effects on the protein expression levels of NQO1 in hippocampus of PND21 male pups and the total and nuclear Nrf2,HO-1 in hippocampus of PND21 female pups.PM2.5 and HFD had synergy effects on the protein expression levels of the total Nrf2,NQO1 in hippocampus of PND42 male pups and HO-1 in hippocampus of PND42 male and female pups.However,PM2.5 and HFD had antagonism effects on the protein expression levels of nuclear Nrf2 in hippocampus of PND60 male pups and HO-1 in hippocampus of PND60 male and female pups?P<0.05?.Compared with CC group,the protein expression levels of NQO1 in hippocampus of PND21 male pups and nuclear Nrf2,HO-1 in hippocampus of PND42,PND60 male pups in H-PM2.5 group were increased,while the protein expression levels of HO-1 in hippocampus of PND60male pups were decreased?P<0.05?.Compared with HFD group,the protein expression levels of total Nrf2,HO-1 in hippocampus of PND21 female pups and total Nrf2 in hippocampus of PND42,PND60 male pups in HFD+H-PM2.5 group were increased,while the protein expression levels of HO-1 in hippocampus of PND42,PND60 female pups were decreased?P<0.05?.Compared with L-PM2.5 group,the protein expression levels of total Nrf2,HO-1,NQO1 in hippocampus of PND21 female pups and PND42 male pups in HFD+L-PM2.5 group were increased,while the protein expression levels of HO-1 in hippocampus of PND42 female pups and nuclear Nrf2 in hippocampus of PND60 male pups were decreased?P<0.05?.Compared with H-PM2.5 group,the protein expression levels of total and nuclear Nrf2 in hippocampus of PND21 female pups and HO-1 in hippocampus of PND42 male pups in HFD+H-PM2.5 group were increased?P<0.05?.Conclusions 1 Co-exposure to PM2.5 and HFD may cause more severely damage of cognitive function in male pups than exposure alone.2 PM2.5 and HFD had synergy effects on Nrf2 signaling pathway-related genes and protein expression levels in hippocampus of rats offspring.3 Nrf2 signaling pathway can control the oxidative stress induced by PM2.5and HFD through up-regulating the expression of downstream target genes HO-1 and NQO1.Nrf2 signaling pathways.Figure 6;Table 39;Reference 101... |
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