The Clock Gene REV-ERBα、RORα And The Inflammasome NLRP3 Were Found In Correlation Of Expression In Peripheral Blood Of Patients With Atrial Fibrillation And Clinical Significance Study

Objective:(1)To study the expression changes of clock genes REV-ERBα,RORα and inflammatory bodies NLRP3 in peripheral blood of patients with atrial fibrillation.(2)Explore the clock gene REV-ERBα、RORα based on the possible mechanism and clinical significance of NLRP3 inflammatory body regulatory pathway involved in the occurrence and development of AF.Methods:A total of 88 patients diagnosed with AF admitted to the Affiliated Hospital of Yangzhou University and Jiangsu North People’s Hospital from 2022.04 to 2022.10 were selected,including 37 patients in the paroxysmal group and 51 in the persistent group,besides,43 healthy patients in physical examination center during the same period as the control group.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect mRNA expressions of peripheral blood clock genes REV-ERBa and RORα,Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of inflammatory body NLRP3 protein in peripheral plasma.General baseline data and laboratory biochemical indicators of subjects in the 3 groups were compared,the Spearman analysis method was used to analyze the correlation of relevant factors;Ordered multi classification logistic regression analysis was used to analyze the factors affecting the occurrence and development of AF;and Receiver operating curve(ROC)to evaluate the auxiliary diagnostic efficacy of REV-ERBα,RORα,NLRP3 and left atrial diameter(LAD)in AF.Results:(1)Comparison of subjects’ general information:gender,BMI value,alcohol consumption,smoking,hypertension,diabetes,fasting blood glucose,TC,TG,HDL,LDL,ALT,AST and Cr had no statistical significance(P>0.05).There were significant differences in age,coronary heart disease ratio,heart failure ratio and LAD(P<0.05).The proportion of coronary heart disease and LAD in PaAF group was higher than that in control group,the difference was statistically significant(P<0.05);the age,proportion of coronary heart disease,proportion of heart failure and LAD in PeAF group was higher than that in control group,the difference was statistically significant(P<0.05);In the two AF subgroups,the heart failure ratio and LAD in PeAF group were higher than those in PaAF group,and the difference was statistically significant(P<0.05).(2)The mRNA expression of clock gene REV-ERBα in AF group was lower than that in control group,and the difference was statistically significant(P<0.01).There was no significant difference in REV-ERBa mRNA between PaAF and PeAF groups.(3)The expression level of RORα mRNA in PeAF group was significantly lower than that in control group and PaAF group(P<0.01),but there was no significant difference between PaAF group and control group.(4)The expression level of NLRP3 inflammasome in PeAF group was significantly higher than that in control group and PaAF group,with statistical significance(P<0.01).There was no significant difference in NLRP3 expression between the control group and the PaAF group.(5)Spearman correlation analysis showed that the mRNA expression level of REV-ERBa was negatively correlated with age(P=0.03,rs=-0.19).There was no significant correlation between the expression levels of RORα and NLRP3 and age(P>0.05).(6)Spearman correlation analysis showed that the mRNA expression levels of clock and genes REV-ERBa and RORα were negatively correlated with LAD size(P<0.01,correlation coefficients rs=-0.43 and rs=-0.24,respectively).The expression level of NLRP3 was positively correlated with LAD size(P<0.01,rs=0.26).(7)Spearman correlation analysis showed that mRNA expression levels of clock genes REVERBα and RORα were negatively correlated with NLRP3 inflammatory body protein expression levels(P<0.001,correlation coefficients rs=-0.49,rs=-0.46,respectively).(8)With the stage of AF disease as the dependent variable and age,coronary heart disease,heart failure,LAD,REV-ERBα,RORα mRNA levels and NLRP3 protein levels as the independent variables,the ordered multi-classification Logistic regression analysis showed that,Chronic heart failure(P=0.029,95%CI(2.204-0.120)],the REV-ERBα[P<0.001,95%CI(1.053 3.298)],NLRP3(P=0.037,95%CI(0.007)0.238)]and LAD[P<0.001,95%CI(0.072-0.245)]were independent risk factors for the occurrence and development of AF disease.(9)AF was used as the state variable and REV-ERBα,RORα,NLRP3 and LAD were used as test variables to conduct ROC curve analysis.The results show that REV-ERBα(AUC=0.8722,CUTOFF value=0.665,sensitivity=0.7126,specificity=0.9524),RORα(AUC=0.6709,CUTOFF value=0.3203,sensitivity=0.4598,specificity=0.8605),NLRP3(AUC=0.6751,CUTOFF value=0.3140,sensitivity=0.5698,specificity=0.7442),LAD(AUC=0.8290,CUTOFF value=0.5740,sensitivity=0.8068,specificity=0.7674)have certain predictive value for AF.Conclusion:1.In patients with atrial fibrillation,the expression of clock genes REV-ERBαand RORα were decreased,and the expression of inflammatory body NLRP3 was increased.2.The expression levels of clock genes REV-ERBα and RORα were negatively correlated with LAD.The expression level of NLRP3 in inflammatory bodies was positively correlated with LAD.3.The mRNA expression levels of clock genes REV-ERBα and RORα were negatively correlated with the NLRP3 expression levels of inflammatory bodies.4.Clock genes REV-ERBα and RORα may be involved in the occurrence and development of AF through inflammation and atrial remodeling mechanisms and have predictive value for the occurrence of AF.