The Study Of Chronic Intermittent Hypoxia On Aorta Of Rabbits And Correlated Mechanism

Object In this research,experiments were carried out on the influence on structure of aorta in OSAHS rabbits,the expression of NF-k B,TNF-αand ICAM-1 protein in aorta;so that we look forward to investigate the possible association between them and to explore the possible effect of atorvastatin on NF-kB,TNF-α,ICAM-1 expression in aorta of CIH rabbits.So it will supply with essential laboratory evidences for the clinical therapy and prevention of atherosclerosis of OSAHS.Methods 1.Establishment of chronic-intermittent hypoxia model in rabbits:twenty-four male New Zealand rabbits were chosen.The twenty-four rabbits were randomly assigned to four experimental groups (n=6/group):A group was a unhandled control group(UG);B group was treated by 12-week intermittent hypoxia(CIH);C group was treated by 8-week intermittent hypoxia and 4-week pause(Pause);D group was treated by 12-week intermittent hypoxia and and intervened by atorvastatin during the later 4 weeks(Atorvastatin);Animals from UC group were raised under physiological conditions,Animals in CIH group were kept in the plexiglass chamber between 9Am-5Pm and underwent intermittent hypoxic challenge(oxygen concentration ranged from lowest 8.5%--21%,8 minutes of each cycle) for 8h/day for 12 weeks.Animals in Pause group were kept in the plexiglass chamber between 9Am-5Pm and underwent intermittent hypoxic challenge(oxygen concentration ranged from lowest 8.5%--21%,8 minutes of each cycle) for 8h/day for 8 weeks, and then were raised under physiological conditions for 4 weeks;Animals in Atorvastatin group were kept in the plexiglass chamber between 9Am-5Pm and underwent intermittent hypoxic challenge(oxygen concentration ranged from lowest 8.5%--21%,8 minutes of each cycle) for 8h/day for 12 weeks,but in the later 4 weeks were given atorvastatin (1.5mg/(kg·d)).Room temperature was 25±1℃,The feedstuff and water were same for all rabbits.Pressure,temperature and humidity inside the plexiglass chamber were standardized.2.The determination of morphology and serology:The rabbits were routinely sacrificed at the end of experiment,the changes of the following indexes were observed:the general pathological changes(HE staining);the expression of NF-kB,TNF-αand ICAM-1 protein in Endothelial cells of aorta(immunohistochemistry staining,SABC stain);Results1.Changes in the tructure of aorta was obvious in chronic intermittent hypoxia group as compared with the unhandled control group:early atherosclerosis appeared--foam cell deposition under Endometrial of aorta.2.The expression of NF-kB,TNF-αand ICAM-1 in aorta in CIH was obviously increased compared with that in UC group(p＜0.05); The expression of NF-kB,TNF-αand ICAM-1 in aorta in Atorvastatin group was obviously decreased compared with that in CIH group(p＜0.05);There was no specific differences of the expression of NF-kB, TNF-αand ICAM-1 in aorta between Atorvastatin group and Pause group.3.There was positive correlation between the expression of NF-kB and TNF-α(r=0.868,P＜0.01);There was positive correlation between the expression of NF-kB and ICAM-1(r=0.836,P＜0.01);There was positive correlation between the expression of TNF-αand ICAM-1 (r=0.751,P＜0.01)。Conclusion 1.chronic intermittent hypoxia can lead to early atherosclerosis in rabbits,which is correlated with the activation of NF-k B and the increased expression of TNF-α,ICAM-1,two important NF-kB -dependent gene product.2.Atorvastatin or provide normal oxygen in later 4 weeks can reverse the early atherosclerosis to some extent,which may be related with the decreased expression of NF-kB,TNF-α,ICAM-1 in Endothelial cells.