The Research On Mechanisms About Vascular Endothelial Impairment Related To Different Styles Chronic Intermittent Hypoxia

Background and objective:OSAS is seemed to be a systemic disease.People with chronic IH are prone tocardiac and vascular damages.Much attention has been paid to endothelialdysfunction,which is regarded as the contributors to vascular diseases.Endothelialdysfunction can induce atherosclerosis,impairment of endothelium-dependentvasodilatation and blood coagulation disorder.The long-standing IH/ROX is the keypathology of Obstructive sleep apnea syndrome (OSAS),Chronic intermittenthypoxemia may be responsible for triggering endothelial dysfunction in OSAS.Butthe mechanism about it is not very clear,so we estimate a model to mime theoccurrence of intermittent hypoxia,investigating the difference of oxidative andinflammatory level of endothelial cell which is exposed in various intermittenthypoxia environments,The purpose is to approach the possible mechanism of CIHrelated vascular endothelial impairment.Contents:1.The research about CIH and oxidative stress,the HUVECs exposed in differentCIH styles2.The research about CIH and oxidoreduction sensitive transcription factors3.The research about CIH and inflammatory factors.Methods:Set up a different intermittent hypoxia environment of HUVECs by computercontrol.Divided different groups by three level oxygen concentration and five IHfrequency.Investigate the level of GSH-PX,MDA,TNF-αand ICAM-1 by ELISAmethod;Detect NF-κB and HIF-1 by Western-Blot,the activity of NF-κB DNAcombination by EMSA.Results: The first part:1.In different IH frequency exposure,the levels of MDA were higher than controland SH group.For GSH-PX,the levels were different to different IH frequency,most of them were higher than control and SH group,but for an exceptionalresult,in the group of 9/h,the level of it was increased markedly than controlgroup.2.In different IH degree,the levels of MDA and GSH-PX were all increased.3.We found the interplay between IH degree and frequency by analysis the 15 CIHstyles4.In the relational analysis of GSH-PX and MDA,we found the negativecorrelation between them.The second part:1.For NF-κB,the concentration in cell plasma had no difference with control andSH group,but in nucleolus,the NF-κB concentration was higher evidently thanother groups.2.For the detecting of the DNA combinational activity of NF-κB,we also foundthe difference in 15 groups and the interplaying between IH degree andfrequency.3.The result of correlation analysis between GSH-PX and the combinationalactivity of NF-κB,the index is r=-0.51,P=0.00,significant negative correlation.4.In the expression of CIH (IH=1.5% O₂,frequency 12/h),we did not find theexpression of HIF-1.5.In the expression of the c-fox mRNA,we found the difference expressionbetween the different IH frequency,the group frequency 12/h was higher thanothers.The third part:1.In the fix up frequency of 12/h,we found the difference levels of TNF-αandICAM-1 between CIH with control and SH groups.2.In the testing ofTNF-αand ICAM-1 in 15 groups,we found the interplay ofIH degree and frequency too. 3.In the correlation analysis of combinational activity of NF-κB to TNF-αandICAM-1,we did not detect significant correlations.Conclusions:1.To HUVECs,the exposure to different CIH styles prone to oxidative stressand inflammatory damages,but we found a exceptional type,which hadprotecting effects.2.The exposure of different CIH styles were with different degrees of vascularendothelial impairment,but the variable trend was irregular.We found theevident interplay effects between IH degree and IH frequency.3.CIH active the inflammatory transcriptional factors selectively,we did notdetect the active of adaptable pathway HIF-1.4.In our research,we consider oxidative stress may be the original factor,which can induce the activation of NF-κB,the link between CIH andinflammatory factors.NF-κB and oxidative stress co-operate to effect therelease of inflammatory factors.