Study On The Correlation Between Plasma S100A1 Calcium Binding Protein Level And Acute Ischemic Stroke And Its Mechanism

AimTo investigate the level of plasma S100A1 calcium binding protein in patients with Acute ischemic stroke(AIS)in the early stage of disease development,and to analyze the correlation between S100A1 and AIS,and to explore whether the mechanism of action of S100A1 protein in the pathogenesis of AIS is related to human NF-κB p65 and human IL-6.Methods(1)161 patients with acute ischemic cerebrovascular disease(AICVD)admitted to the brain center of Subei people’s Hospital of Jiangsu Province from April 2020 to November 2020 were selected as the research objects,including 141 patients with Acute ischemic stroke(AIS)and 20 patients with transient ischemic attack(TIA),and 31 healthy controls(HC)were collected from the health examination center of our hospital.Patients were screened according to different inclusion and exclusion criteria.The basic clinical data of the subjects were collected,including general information of the subjects:age,BMI,gender,smoking history and drinking history;personal history:history of hypertension,diabetes,hyperlipidemia,atrial fibrillation and coronary heart disease.Related examinations were collected after admission,including physical examination judgment at admission:NIHSS,systolic blood pressure,diastolic blood pressure and toast classification.Fasting venous blood samples of patients with Acute ischemic stroke were collected in the morning of the second day after admission,and plasma tests were taken,including blood routine indexes(red blood cells,hematocrit,white blood cells,neutrophils,lymphocytes,monocytes,red blood cell distribution width and platelets);biochemical indexes(fasting blood glucose,TC,TG,LDL-C,HDL-C,creatinine,ALT,AST and homocysteine);plasma indexes(S100A1,NF-κB p65 and IL-6).(2)The fasting venous blood samples of patients with Acute ischemic stroke were collected in the morning of the second day after admission.The control group was completed in the health examination center of the hospital.Part of the plasma was retained and stored in-80℃ refrigerator for standby,and the rest was sent to the hospital test center.(3)The levels of S100A1 calcium binding protein(S100A1),human nuclear factor p65(NF-κB p65)and human interleukin-6(IL-6)in plasma were detected by ELISA kit.(4)According to the Pulicino formula,the cerebral infarction volume was calculated by CT and MRI.In small volume cerebral infarction(SCI)group,the total infarct volume was less than 5cm3;in medium volume cerebral infarction(MCI)group,the total infarct volume was 5-10cm3;in large volume cerebral infarction group,the total infarct volume was less than 5cm3.According to the criteria,they were divided into SCI group,MCI group and LCI group.(5)The patients were followed up for 3 months after the onset of the disease,and were divided into groups according to Rankin’s modified scale score;MRS:<3 was divided into good prognosis group,MRS:≥ 3 was divided into poor prognosis group.(6)To investigate the level of S100A1 protein in the plasma of acute ischemic cerebrovascular disease;The difference of plasma S100A1 in AIS group,TIA group,HC group and AIS group was compared among different infarction size subgroups;The correlation between S100A1 protein and cerebral infarction volume was analyzed.To explore the diagnostic value of S100A1 protein in the short-term prognosis of patients with AIS,and to analyze the association among plasma S100A1,NF-κB p65 and IL-6,so as to explore the potential mechanism of S100A1 protein in AIS.(7)All data were statistically analyzed by Spss.26 software.Results1.Distribution of research objects:A total of 192 subjects were included,including 141 in the AIS group,20 in the TIA group and 31 in the HC group.According to different cerebral infarction volume,the Acute ischemic stroke group was further divided into SCI group(n=78),MCI group(n=32)and LCI group(n=31).In accordance with the improved Rankin grading scale,there were 80 patients in Favorable prognosis group(FP)and 61 patients in Unfavourable prognosis group(UP).2.Objective to explore the plasma S100A1 protein level in acute ischemic cerebrovascular disease:Comparison of Acute ischemic stroke group(AIS),transient ischemic attack group(TIA)and healthy control group(HC):In terms of baseline data,except the admission systolic blood pressure was statistically significant(P<0.05),other baseline data showed no significant statistical significance(P>0.05).In terms of laboratory test indicators,in addition to the statistical significance of white blood cells,monocytes,platelets,creatinine and ALT(P<0.05),after pairwise comparison,it was found that the levels of white blood cells,monocytes,platelets,and creatinine in the AIS group were higher,While the levels of ALT were lower than those in the HC group(P<0.05).Meanwhile,the levels of monocytes and platelets in AIS group were higher than those in TIA group(P<0.05),while the levels of ALT were lower than those in TIA group(P<0.05).No obvious statistical significance was found in other laboratory test indexes(P>0.05).Plasma S100A1,NF-K B p65 and IL-6 between AIS group,TIA group and HC group were statistically significant(P<0.05).The comparison between the groups indicated that the levels of the AIS group were significantly higher than those of the TIA group and HC group(P<0.05),but there was no significant statistical significance between TIA group and HC group(P>0.05).The Area under ROC curve(AUC)of plasma S100A1 for the diagnosis of AIS was 0.818(P<0.05,95%CI 0.749-0.887),and when the Optimum cutoff value(Cut off)was 181.03,the Maximum Youden index(Jmax)was 0.578 and sensitivity(Se)was 95.0%.Specificity(Sp)was 62.7%.The AUC of plasma S100A1 for the diagnosis of TIA was 0.720(P<0.05,95%CI 0.592-0.848).When Cut off was 150.14,the Jmax,Se and Sp were 0.442,50.0%and 94.2%respectively.3.Objective to explore the correlation between plasma S100A1 level and the different infarct volumes of Acute ischemic stroke:(1)Comparison among Small volume cerebral infarction group(SCI),Medium volume cerebral infarction group(MCI)and Large volume cerebral infarction group(LCI):In terms of baseline data,in addition to admission NIHSS,there was statistical significance(P<0.05),the comparison between groups indicated that the admission NIHSS level of LCI group was higher than that of SCI group and MCI group(P<0.05);the other baseline data had no significant statistical significance(P>0.05).In terms of laboratory test indexes,except for ALT and AST,the comparison between groups indicated that the levels of ALT and AST in LCI group were higher than those in SCI group(P<0.05);the other laboratory indexes were not statistically significant(P>0.05).There were significant differences in S100A1,NF-κB p65 and IL-6 among SCI group,MCI group and LCI group(P<0.05).The level of LCI group was significantly higher than that of MCI group and SCI group(P<0.05),but there was no significant difference between MCI group and SCI group(P>0.05).(2)Correlation between plasma S100A1 and infarct size:There was no significant positive correlation between S100A1 and cerebral infarction volume(r<0.3),but there was significant difference(r=0.259,P<0.05)4.To investigate the correlation between plasma S100A1 level and prognosis of acute cerebral infarction:(1)Comparison of baseline data between the group with Favorable prognosis(FP)and the group with Unfavorable prognosis(UP):In terms of baseline data,there was statistical significance in NIHSS(P<0.05),but there was no statistical significance in other baseline data(P>0.05).In terms of laboratory test indicators,TG level in FP group was higher than that in UP group,with significant difference(P<0.05).The levels of HDL-C,AST,homocysteine,IL-6 and S100A1 in UP group were higher than those in FP group,with statistical significance(P<0.05).There was no significant statistical significance in other laboratory tests(P>0.05).(2)Binary Logistic regression analysis indicated that S100A1 was an independent risk factor for predicting poor prognosis in patients with acute cerebral infarction at 3 months.5.Objective to explore the correlation analysis of plasma S100A1,NF-κB p65 and IL-6:There was a positive correlation between plasma S100A1 and IL-6,with statistical significance(r=0.353,P<0.05).There was no significant positive correlation between plasma S100A1 and NF-κB p65(r<0.3),but it was statistically significant(r=0.290,P<0.05).There was a positive correlation between plasma IL-6 and NF-κB p65,and there was statistical significance(r=0.313,P<0.05).Conclusions1.Plasma S100A1 protein may have a better diagnostic effect on AIS and TIA.When S100A1≥181.03pg/ml,it may be more likely to be diagnosed as AIS,and when S100A1≤150.14pg/ml or S100A1≤181.03pg/ml,it may be more likely to be diagnosed as TIA.2.Plasma S100A1 protein was correlated with the infarct volumes of AIS to some extent,and its level reflected the severity of acute cerebral infarction to some extent.3.Plasma S100A1 protein is associated with short-term prognosis of AIS and may be an independent risk factor for predicting poor prognosis in patients with acute cerebral infarction at 3 months.4.Plasma S100A1 protein levels were correlated with IL-6 and NF-κB p65,suggesting that S100A1 protein might mediate inflammatory response through TLR4/NF-κB pathway in acute cerebral infarction.