The Study On The Role Of Interleukin-33 And Its Signal Pathway In Obstructive Sleep Apnea Hypopnea Syndrome

Objective:To explore the expression of interleukin-33(IL-33)and its receptor soluble growth stimulation expressed gene 2(sST2)in the plasma of patients with obstructive sleep apnea hypopnea syndrome(OSAHS).To understand the expression levels of IL-33/ST2L classic signaling pathway related genes in peripheral blood mononuclear cell(PBMC)of patients with OSAHS.To explore the role of IL-33 and its signaling pathway in OSAHS.To explore the possibility of IL-33 as a marker for the diagnosis of OSAHS.Methods:Enrolled 22 non-OSAHS patients,mild-moderate OSAHS patients,and severe OSAHS patients,and collected their clinical data.Polysomnography was monitored overnight,and 5ml of peripheral blood was collected the next morning.Enzyme-linked immunosorbent assay(ELISA)was used to detect concentration of plasma IL-33 and sST2.PBMCs were separated,total RNA was extracted,and then real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression of IL-33/ST2L classical signaling pathway related genes.IBM SPSS Statistics 22.0 and GraphPad Prism 8 statistical software were used to analysis.Correlation analysis was used to analyze the relationship between the concentration of IL-33,sST2 and various indicators in each group of patients.Logistic regression analysis was used to predict the risk factors of OSAHS.At the same time,receiver operating characteristic curve(ROC)was used to analyze the efficacy of OSAHS diagnosis.Results:1.There was no significant difference in age and gender between of three groups of study subjects(P>0.05).There were statistically significant differences in body mass index(BMI),apnoea hypopnea index(AHI),lowest oxygen saturation(LSpO2),mean oxygen saturation(MSpO2),minimum heart rate,and average heart rate among the three groups(all P<0.01).2.The expression of activator protein 1(AP-1)mRNA,nuclear factor kappa B(NF-κB)mRNA,and tumor necrosis factor receptor-related factor 6(TRAF6)mRNA in PBMCs in the mild-moderate group and the severe group were lower than those in the non-OSAHS group(P<0.05),there was no statistically significant difference between the mild-moderate group and the severe group(P>0.05).The expression of ST2L mRNA in the severe group was significantly lower than that in the non-OSAHS group(P<0.01),but there was no statistically significant difference between the mild-moderate group,the severe group,and the non-OSAHS group(all P>0.05).The expression of IL-33 mRNA in the severe group was higher than that in the non-OSAHS group(P<0.001)and the mild-moderate group(P<0.05),but there was no significant difference between the non-OSAHS group and the mild-moderate group(P>0.05).The expression of plasma IL-33 and sST2 concentrations in the mild-moderate group and the severe group were higher than those in the non-OSAHS group(P<0.01),but there was no significant difference between the mild-moderate group and the severe group(P>0.05).3.Correlation analysis shows that the concentration of IL-33 in plasma was significantly positively correlated with AHI and sST2 concentrations(all P<0.001),and negatively correlated with LSpO2,MSpO2,ST2L mRNA(all P<0.05),and no correlation with BMI(P>0.05).The concentration of sST2 in plasma was significantly positively correlated with AHI(P<0.001),was significantly negatively correlated with LSpO2,MSpO2,and ST2L mRNA(P<0.01),and had no correlation with BMI(P>0.05).4.Binary Logistic regression analysis showed that BMI,IL-33 concentration,and sST2 concentration were independent influencing factors in OSAHS patients.5.ROC curve analysis showed that the sensitivity of IL-33 and sST2 in screening OSAHS patients was 83.72%and 68.18%,the specificity was 80%and 95.24%,and the area under the curve(AUC)was 0.880 and 0.864,respectively.Conclusion:1.As the severity of OSAHS patients inereases,the more severe the hypoxia,the higher the expression of IL-33,so IL-33 may be involved in the occurrence and development of OSAHS.2.The sST2 receptor and ST2L receptor competitively bind IL-33.The IL-33/ST2L classic signaling pathway is inhibited in OSAHS patients,preventing the further expansion of inflammation.The sST2 receptor may play an important role in the process of protecting OSAHS from inflammatory damage.3.IL-33 has a good diagnostic value for OSAHS,and it is expected to be used as a biomarker for the diagnosis of OSAHS.