Expression Of IL-33 In CSF And Plasma After Aneurysm Subarachnoid Hemorrhage And Its Clinical Significance

BACKGROUND: Subarachnoid hemorrhage(SAH)is a serious cerebrovascular disease characterized by high morbidity and lethality.About85% of cases are caused by ruptured intracranial aneurysms,also known as arteries Aneurismal subarachnoid hemorrhage(aSAH).More and more studies have shown that inflammatory reaction is involved in brain damage,blood-brain barrier destruction,cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage,which is a key factor leading to poor prognosis.As a new member of interleukin-1 family,IL-33 is closely related to inflammation.Animal experiments have shown that the expression of IL-33 after SAH may play an important role in neuroinflammation and remains to be further studied.PURPOSE: The aim of this study was to analyze the expression of IL-33,its receptor ST2 and the inflammatory factor TNF-? in plasma and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage(aSAH).The difference of IL-33 levels in the plasma at different time points after onset was analyzed to explore the changes of IL-33 levels in the course of the disease over time.The level of IL-33 expression in patients with neurological grading,cerebral vasospasm and clinical Prognosis,and explore its value in determining the severity of the disease and assessing the prognosis.METHOD:1.The research object: March 2016-March 2017,our hospital neurosurgery patients with aneurysmal subarachnoid hemorrhage as theexperimental group.Patients admitted to the hospital within 72 hours of onset and concurrent craniotomy occlusion were included in the experimental group while excluding previous neurological diseases such as stroke,Alzheimer's disease and meningitis;previous autoimmune diseases such as Rheumatoid arthritis,bronchial asthma,systemic lupus erythematosus,autoimmune spondylitis,etc;and patients with severe damage to cardiopulmonary,hepatic and renal systems.A total of 36 patients were included in this study.The same period in our hospital physical examination of 12 healthy volunteers,excluding neurological diseases,as a blood control group.The same period in our hospital orthopedic spinal anesthesia in the lower extremity fixation removal of 12 patients,excluding neurological disease as a control group of cerebrospinal fluid.2.Specimen collection: 1)The experimental group was complete preoperative preparation of craniotomy aneurysm occlusion,the routine lumbar drainage catheter drainage,retention of 1ml cerebrospinal fluid;at the same time after the onset of d1,d3,d7,d14 extraction Peripheral venous blood 2ml.The concentrations of IL-33,ST2 and TNF-? in CSF and plasma were detected by enzyme linked immunosorbent assay(ELISA).2)Peripheral venous blood 2 ml were randomly selected from plasma control group,and the concentrations of IL-33,ST2 and TNF-? in plasma were still detected by ELISA.3)Cerebrospinal fluid of cerebrospinal fluid was randomly selected from 1 ml of cerebrospinal fluid,and the concentrations of IL-33,ST2 and TNF-? in CSF were detected as before.At the same time,the general data such as the age and gender of the experimental group were collected,and the clinical data of Hunt-Hess grade,modified Fisher grade and WFNS score on admission were collected.3.Judgment of cerebral vasospasm: In experimental group,mean blood flow velocity of middle cerebral artery was measured by transcranial Doppler ultrasound(TCD)3-7 days after onset,mean blood flow velocity(mBFV)erimental group,mean blood flow velocie of cerebral vasospasm(CVS).4.Prognosis analysis: The experimental group was followed up for 3months postoperatively or by telephone,and the modified Rankin score(MRS)was used to evaluate the prognosis of the patients.5.Statistical analysis: The data obtained from the test were expressed as mean ± standard deviation,t-test was used to compare the two groups,and single-factor analysis of variance was used to compare the multiple groups.The qualitative data were compared by chi-square test.In the correlation analysis,Pearson correlation coefficient was used for continuous variables and Spearman correlation coefficient was used for non-continuous variables.The clinical prognosis of patients with IL-33 levels in plasma and cerebrospinal fluid was evaluated by binary logistic regression analysis.Definition P <0.05 for the difference was statistically significant,P> 0.05 for the difference was not statistically significant.RESULTS:1)The levels of IL-33,ST2 and TNF-?in plasma of patients with aSAH were significantly higher than those in healthy controls.The concentrations of IL-33 and ST2 in plasma were dynamic after onset and began to increase on the first day after onset,Then rose to the peak on the third day and then decreased to the 14 th day after the onset of the disease.The levels of IL-33 in the experimental group and the control group on the 3rd and 7th day,ST2 level on the 3rd and 7th day,3 days TNF-? levels were statistically significant(P <0.05).2)The level of TNF-? in CSF of aSAH patients was significantly higher than that of the control group(P <0.01).However,the levels of IL-33 and ST2 in the CSF of the experimental group were not significantly different from those in the control group P> 0.05).3)The correlation between cytokines suggested that plasma IL-33 and TNF-? had a weak correlation at day 1 and 14(r =-0.438,P <0.05 on the first day;on the 14 th day,r =-0.36,P <0.05).There was a strong correlation between IL-33 and ST2 on the 14 th day(r = 0.652,P <0.01).4)The correlation analysis of plasma levels of IL-33,ST2 and TNF-?in patients with aSAH and clinical indicators suggested that Hunt-Hess grade on admission and IL-33 level on the third day(r =-0.705,P < 0.05),ST2 level(r=-0.654,P <0.05)on the third day,the difference was statistically significant.There was a significant correlation between WFNS grade on admission and IL-33 level on the seventh day(r =-0.683,(r = 0.671,P <0.01).The MRS score at the third month after operation was significantly correlated with the level of IL-33 on the third day(r = 0.665,P <0.05),TNF-? level on the first day(r =-0.782,P <0.05),the difference was statistically significant;Subgroup analysis showed a good prognosis group(MRS?4)was higher than that of the poor prognosis group in the 1-14 day of the level of plasma IL-33(MRS?3),the difference was statistically significant in third days(P < 0.01).5)Univariate logistic regression analysis showed that the prognosis was good and the prognosis was poor.The results showed that Hunt-Hess grade,WFNS grade,improved Fisher grade,IL-33 level on the third day,ST2 level on the third day,(P <0.05).The results of multivariate logistic regression analysis indicated that the level of lL-33 on day 3 could be an independent factor in predicting the prognosis of patients with aneurysmal subarachnoidhemorrhage(OR,0.938;95% CI,0.821-0.973,P = 0.021).Hunt-Hess grade,WFNS grade,improved Fisher grade and TNF-? level on the third day also could be used as independent prognostic factors.CONCLUSION:1.The level of plasma IL-33 is associated with aneurysmal subarachnoid hemorrhage and may be an independent protective factor.2.The level of plasma IL-33 is related to the prognosis of aneurysmal subarachnoid hemorrhage,which may be an independent factor to predict its prognosis.