The Expression And Correlation Of Circadian Clock Genes And HIF-1α In Patients With Hypertension Complicated With OSAHS

Part Ⅰ The expression of circadian clock genes in patients with hypertension complicated with OSAHSObjective:The occurrence of acute cardiac adverse events is highly correlated with circadian rhythm,and the change of onset time often indicates abnormal expression of circadian clock genes.At present,most patients with hypertension still have abnormal circadian rhythm of blood pressure which fails to meet the standard.Most of these patients are complicated with OSAHS,and the prognosis of cardiovascular disease is relatively poor.Therefore,it is difficult to achieve the ideal blood pressure levels only by adjusting the time of administration.Understanding the differences in the overall expression of circadian clock genes is an effective measure to control blood pressure rhythm.Using circadian clock genes as drug therapy targets is expected to simulate normal circadian rhythm and improve adverse blood pressure phenotype.This research explored the expression levels of circadian clock genes in patients with hypertension and hypertension complicated with OSAHS with a view to providing new intervention and treatment targets for hypertension.Research methods:Case-control study method,using real-time fluorescent quantitative PCR technology(quantitative real-time polymerase chain reaction,qRT-PCR)to determine the relative expression of the core clock genes of BMAL1,CLOCK,PER1,PER2,CRY1,REVmRNAs in 36 healthy men,36 hypertension patients and 36 patients with hypertension complicated with OSAHS.Besides,the basic information and related laboratory index data of those who are mentioned above are collected to conduct statistical analysis,which aims at studying the expression differences of relevant core circadian clock genes in patients with hypertension complicated with OSAHS.Research results:1.Statistical analysis of clinical data showed that in 108 subjects,BMI,GLU,TG,TC,LDL and HDL levels in hypertension group and hypertension combined with OSAHS group were significantly higher than those in the control group(P<0.01).2.The statistical analysis of 24h dynamic blood pressure monitoring showed that the rate of non-dipper blood pressure in 72 hypertension patients was 33.3%,and the rate of non-dipper blood pressure in the hypertension complicated with OSAHS group was 75%.Among them,the phenotype of non-dipper blood pressure,night SBP,night DBP and blood pressure load in the hypertension group and the hypertension complicated with OSAHS group were significantly higher than those in the control group(P<0.05);24h SBP and daytime SBP of subjects with hypertension complicated with mild OSAHS,moderate OSAHS and severe OSAHS were compared,and the differences were statistically significant(P<0.05).3.The analysis of ESS score and PSG monitoring in hypertension complicated with OSAHS group showed that the differences in ESS score,AHI,AP1,AP2 and LAST among patients with hypertension complicated with mild OSAHS,moderate OSAHS and severe OSAHS were statistically significant(P<0.01).4.Immune fluorescence quantitative experimental analysis showed that compared with the control group,the related core circadian clock genes expression of BMAL1,CLOCK,PER1,PER2 and CRY1,REVmRNAs were the lowest in hypertension with OSAHS group(P<0.01),and the BMAL1,PER2 and REV mRNAs expressions were relatively low in hypertension group(P<0.05).In addition,the CLOCK,PER1 and CRY1mRNAs expressions in hypertension group showed no significant statistical difference.Conclusion:The core circadian clock genes can be involved in the regulation of circadian blood pressure rhythm.Patients with hypertension,especially those with hypertension combined with OSAHS are more likely to be complicated with glucose and lipid metabolism disorder and abnormal circadian blood pressure rhythm.With increased levels of hypoxia,the related core circadian clock genes expression is disrupted.Part Ⅱ Expression of hypoxia-inducing factor HIF-1 a and related circadian clock genes in patients with hypertension complicated with OSAHS and its correlation.Objective:HIF-1α and circadian clock genes are a pair of interacting molecules that play an important role in the pathogenesis of hypertension and OSAHS.The purpose of this study was to further explore the correlation between HIF-1α and the expression of the circadian clock genes with the clinical samples.Research methods:In this case-control study,quantitative real-time polymerase chain reaction(qRT-PCR)was used to determine the relative expression levels of HIF-1α mRNAs in 36 healthy subjects and 36 hypertension patients with OSAHS.Based on the above studies,the correlation between HIF-1α and related core clock gene expression was further verified.Research results:1.Compared with the control group,the expression level of HIF-1αmRNAs was significantly decreased in the group of hypertension complicated with OSAHS,with statistical significance(P<0.01).2.The mRNAs expression levels of related core circadian clock genes(BMAL1,CLOCK,PER1,CRY1)were positively correlated with the mRNA expression levels of HIF-1α,with statistically significant differences(P<0.05).In addition,there was no statistically significant difference in the mRNA expression levels of PER2,REV and HIF-1α.Conclusion:In patients with hypertension complicated with OSAHS,the expression of circadian clock genes are disturbed,which may be mediated by HIF-1α.The increase of HIF-1 α may be related to the overexpression of circadian clock genes about BMAL1,CLOCK,PER1,CRY1 mRNAs.