| ObjectiveTo study the mechanism that OSAS promotes the occurrence of cognitive dysfunctions by established Sprague- Dawley rat model of chronic intermittent , the effects of CIH on the expression of RAGE and LRP1 in blood-brain barrier of rat and to explore their role in the development of cognitive dysfunctions.MethodExperiments were performed on 50 three- month- old male Sprague- Dawley rats, they were randomly assigned to three experimental groups: chronic intermittent hypoxia group (CIH,n=20), and unhandled control group (UC,n=15),air control group(AUC,n=15). The rats in UC group were raised normally ,rats in CIH group were placed in a chamber and exposed to intermittent hypoxia and rats in AUC were placed a sealed chamber but not exposed to intermittent hypoxia(in order to avoid interference of Carbon dioxide retention). Rats' learning and memory function were assessed using Morris water-maze test at the end of the experiments. Immunohistoehemical teehniques (PV - 9000 two-step method) were used to test the expression of RAGE and LRP1 in blood-brain barrier and Image-ProPlus software used to determine the mean optical density (MOD) of immunohistochemical Image. Then use SPSS17.0 which is statistical analysis software to analyze these data.Results(1)Morris water maze test learning scores:Place Navigation:After 5 days training ,the escape latency in CIH rats was significantly longer than that in UC rats and AUC rats (P<0.05);There was no significant difference between the escape latency of UC rats and AUC rats(P﹥0.05). Spatial Exploration:to compare with UC group and AUC group ,the frist time passing hide plateform prolonged significantly in CIH rats(P<0.05)and the times acrossing crossing plateform of CIH rats were declined(P<0.05).(2)①Comparing with the positive rate of RAGE protein in UC and AUC rats′endothelial cells and microglia of the BBB,that in CIH was 70%and was significantly higher than their positive rate(26.7%;33.3%) in UC rats′and AUC rats′, there were the significant differences(P<0.05). The expression of RAGE(MOD value) has significantly increased( P<0.05)②The positive rate of LRP1 protein in UC rats′endothelial cells and microglia of the BBB was 33.33%, was significantly lower than its positive rate(73.33%) in UC rats′and AUC rats′,but the LRP1 has decreased in blood-brain barrier.( 3 )The corrlation between expression of RAGE and Morris water maze test learning scores:①The expression of RAGE and escape latency in rats was positively correlated( r=0.658,P<0.05).②The expression of RAGE and the frist time passing hide plateform was positively correlated (r=0.328,p<0.05).③There was negative correlation between the expression of RAGE and the times acrossing crossing plateform(rs=-0.488,p<0.05).( 4 ) The corrlation between expression of LRP1 and Morris water maze test learning scores:①The expression of LRP1 and escape latency in rats was negatively correlated( r=-0.483,P<0.05).②The expression of LRP1 and the frist time passing hide plateform was negatively correlated (r=-0.484,p<0.05).③There was positive correlation between the expression of LRP1 and the times acrossing crossing plateform(rs=0.643,p<0.05).Conclusion1,After the treatment of chronic intermittent hypoxia,the rats′Morris water maze test learning scores were bad, suggesting that Chronic intermittent hypoxia could lead to cognitive impairment of the rats.2,The expression of RAGE protein in endothelial cells and microglia of the BBB of the rat treated by chronic intermittent hypoxia was significantly higher than that not be by treated by chronic intermittent hypoxia, suggesting that chronic intermittent hypoxia may up-regulate transcription or expression of the gene of RAGE. 3,The expression of LRP1 protein in endothelial cells and microglia of the BBB of the rat treated by chronic intermittent hypoxia was significantly lower than that not be by treated by chronic intermittent hypoxia, suggesting that chronic intermittent hypoxia may down-regulate transcription or expression of the gene of LRP1.4,The expression of RAGE in endothelial cells and microglia of the BBB was positively correlated with degree of cognitive impairment for rats,suggesting that RAGE may be play a promotive role in the occurrence and development of cognitive impairment. The expression of LRP1 in endothelial cells and microglia of the BBB was negative correlated with degree of cognitive impairment,suggesting that LRP1 may be protective effect on cognitive function.
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