Study On The Levels Of Occludin And Syndecan-1 In The Serum Of Patients With Anterior Circulation Acute Ischemic Cerebrovascular Disease And Related Mechanisms

Objective To detect the levels of occludin(OCLN)and syndecan-1(SDC-1)in the serum of patients with anterior circulation acute ischemic cerebrovascular disease(ACAICVD).To analyze the correlations between serum OCLN and SDC-1 levels and ACAICVD.Meanwhile,to investigate whether OCLN and SDC-1 degraded from blood-brain barrier to the peripheral blood circulation were related to matrix metalloproteinase-9(MMP-9)and tissue inhibitor of matrix metalloproteinase-1(TIMP-1).Methods(1)A total of 117 patients with ACAICVD(including anterior circulation acute cerebral infarction and transient ischemic attack)who were admitted within 24 hours after onset in the Neurology Department of Northern Jiangsu People's Hospital from March 2019 to November 2019 were collected as the research objects.At the same time,35 cases of health checkups in the physical examination center during the same period were collected as the control group.Collect baseline data of all included objects(containing gender,age,BMI index,smoking history,drinking history,history of hypertension,diabetes history,history of hyperlipidemia,history of cerebral infarction,history of coronary heart disease,history of atrial fibrillation,time from onset to admission,admission NIHSS scores and TOAST classification,etc.);(2)Cerebral MRI or CT examination was performed on all patients,and the volume of cerebral infarction was calculated based on the imaging results.Following the grouping criteria of "infarct volume <5cm3 for small infarction,5cm3? infarct volume ?10cm3 for medium infarction,and infarct volume >10cm3 for large infarction",the patients with anterior circulation acute cerebral infarction were divided into the small infarction group,the middle infarction group and the large infarction group;(3)All discharged patients were followed up and evaluated the m RS scores at 90 days after onset.Following the grouping criteria of " 0 ? m RS scores ? 2 for good prognosis,and m RS scores >2 for poor prognosis",the patients with anterior circulation acute cerebral infarction were divided into the good prognosis group and the poor prognosis group;(4)Fasting elbow venous blood was collected of all patients in the next morning after admission,and blood samples from the control group were collected at the physical examination center.Some blood samples were centrifuged to extracted the serums which were frozen at-80 ? later for future use,and the rest were sent to the central laboratory for examination;(5)The blood routine(including the number of white blood cells,the number of neutrophils and its percentage,the number of lymphocytes and its percentage,the number of monocytes and its percentage)and the levels of hypersensitive C-reactive protein were measured for each research object.And serum OCLN,SDC-1,MMP-9 and TIMP-1 levels were measured by ELISA;(6)The correlations between the levels of serum OCLN and SDC-1 and ACAICVD was discussed by comparing the differences of them among the anterior circulation acute cerebral infarction group,the anterior circulation transient ischemic attack group and the healthy control group,and among the subgroups of patients with anterior circulation acute cerebral infarction,drawing their respective ROC curves and analyzing their correlations with admission NIHSS scores.Moreover,the possible pathological mechanism of OCLN and SDC-1 degraded from blood-brain barrier to the peripheral blood circulation was explored by analyzing their correlations with MMP-9,TIMP-1 and MMP-9 / TIMP-1.The all obtained data were analyzed and processed by SPSS 22.0 package.Result1.Distribution of the research objects:A total of 152 patients were included in the study,containing 35 cases in the health control(HC)group,21 cases in the anterior circulation transient ischemic attack(ACTIA)group,and 96 cases in the anterior circulation acute cerebral infarction(ACACI)group;referring to two different subgroup classification criteria,the patients in the ACACI group were further divided into 39 cases in the small infarction(SI)group,28 cases in the medium infarction(MI)group,and 29 cases in the large infarction(LI)group or 50 cases in the good prognosis(GP)group,and 46 cases in the poor prognosis(PP)group.2.To investigate the correlation between serum OCLN and SDC-1 levels and events of anterior circulation acute ischemic cerebrovascular disease:(1)Comparisons among the ACACI group,the ACTIA group and the HC group:In terms of baseline data,the only statistical difference was founded in the history of atrial fibrillation(P<0.05),and other indicators were similar among the three groups(P>0.05).Routine blood examination showed that there were statistical differences in the number of white blood cells,the number of neutrophils and its percentage,the percentages of lymphocytes,and the number of monocytes among the three groups(P<0.05).Multiple comparisons between the groups in pairs showed the percentages of lymphocytes of the ACACI group was significantly lower than the HC group(P<0.05)while the other indicators of the ACACI group were significantly higher than the HC group(P<0.05),but there was no statistical difference in all above indicators between the other groups in pairs(P>0.05).Hypersensitive C-reactive protein also significantly differed among the three groups(P<0.05).After comparison in pairs,we found the ACACI group was significantly higher than the ACTIA group and the HC group(P<0.05),but there was no statistical difference between the ACTIA group and the HC group(P>0.05).The levels of serum OCLN,SDC-1,MMP-9 and MMP-9 / TIMP-1were statistically different among the three groups(P<0.05).Pairwise comparison showed that all four indicators of the ACACI group were significantly higher than the ACTIA group and the HC group(P<0.05),but there was no statistical difference between the ACTIA group and the HC group(P>0.05).(2)Evaluation of the diagnostic efficacy of serum OCLN and SDC-1 levels: According to receiver operating characteristic(ROC)curve of ACACI which was drawn with serum OCLN concentration,we found that the area under curve(AUC)was 0.755(P<0.05,95%CI 0.668-0.843),and thought that serum OCLN levels had the moderate diagnostic value for ACACI(0.7<AUC?0.85);further calculation shown that the best diagnostic cutoff value was 8.38 ng / ml,the sensitivity was 57.3%,and the specificity was 88.6%.As for ROC curve of ACACI which was drawn with serum SDC-1 concentration,the AUC was 0.658(P<0.05,95%CI 0.557-0.758),which suggested that serum SDC-1 levels had the slight diagnostic value for ACACI(0.5<AUC?0.7);further calculation shown that the best diagnostic cutoff value was1.64 ng / ml,the sensitivity was 58.3%,and the specificity was 74.3%.However,the AUC of ROC curve of ACTIA drawn with serum OCLN concentration was 0.631(P>0.05,95%CI 0.477-0.786),which suggested that serum OCLN levels had no statistically significant diagnostic value for ACTIA.And the AUC of ROC curve of ACTIA drawn with serum SDC-1 concentration was 0.522(P>0.05,95%CI0.364-0.679),which suggested that serum SDC-1 levels also had no statistically significant diagnostic value for ACTIA.3.To investigate the correlation between serum OCLN and SDC-1 levels and the severity of anterior circulation acute cerebral infarction:(1)Comparisons among the SI group,the MI group and the LI group:In terms of baseline data,there were statistical differences among the three groups in gender,history of atrial fibrillation,admission NIHSS scores,and TOAST classification(P<0.05),and there was no statistical difference in the other indicators(P>0.05).Routine blood examination was similar among the three groups(P>0.05).However,hypersensitive C-reactive protein was statistically different among the three groups;multiple comparisons between the groups in pairs showed the LI group was significantly higher than the MI group and the SI group(P<0.05),and the MI group was also significantly higher than the SI group(P<0.05).There were significant differences in the levels of serum OCLN,SDC-1,MMP-9 and MMP-9 / TIMP-1among the three groups(P<0.05).After the pairwise comparisons,it was found that the levels of serum OCLN,MMP-9 and MMP-9 / TIMP-1 of the LI group were significantly higher than the MI group and the SI group(P<0.05),and the MI group was also significantly higher than the SI group(P<0.05);the serum SDC-1 level of the LI group was significantly higher than the MI group and the SI group(P<0.05)),but there was no statistical difference between the MI group and the SI group(P>0.05).(2)Correlations of serum OCLN and SDC-1 with admission NIHSS scores:There was moderate positive correlation(0.5??r?<0.8)between serum OCLN and admission NIHSS scores(r = 0.551,P<0.05).Besides,serum SDC-1 had slight positive correlation(0.3? ? r ? <0.5)with admission NIHSS scores(r = 0.305,P<0.05).4.To investigate the correlation between serum OCLN and SDC-1 levels and the prognosis of anterior circulation acute cerebral infarction—— Comparisons between the GP group and the PP group:In terms of baseline data,patients in the GP group had smaller age,more history of atrial fibrillation,higher proportion of stroke of small vessel occlusion in TOAST classification,lower admission NIHSS scores,and lower proportion of medium and large infarction compared to the PP group,and the differences were significant(P<0.05).There was no statistical difference in blood routine examination between the two groups(P>0.05);hypersensitive C-reactive protein of the GP group was lower than that in the PP group,and the difference was significant(P<0.05).The levels of serum OCLN,MMP-9 and MMP-9 / TIMP-1 of the GP group were lower than those in the PP group,and the differences were significant(P<0.05);there was no statistical difference in serum SDC-1 levels between the two groups(P>0.05).5.To investigate the possible pathological mechanism of OCLN and SDC-1 degraded from blood-brain barrier to the peripheral blood circulation——Correlations of serum OCLN and SDC-1 with MMP-9,TIMP-1,and MMP-9 / TIMP-1:There were moderate positive correlations(0.5??r?<0.8)between serum OCLN and MMP-9(r = 0.681,P<0.05),and MMP-9 / TIMP-1(r = 0.590,P<0.05).Besides,serum SDC-1 had slight positive correlations(0.3??r?<0.5)with MMP-9(r = 0.430,P<0.05),and MMP-9 / TIMP-1(r = 0.352,P<0.05).However,there was no correlation(?r?<0.3)between serum OCLN and SDC-1 and TIMP-1(r = 0.181,P<0.05;r =0.161,P<0.05).Conclusion1.Serum OCLN and SDC-1 levels were related to the severity and prognosis of anterior circulation acute cerebral infarction.The levels of serum OCLN and SDC-1 in patients with anterior circulation acute cerebral infarction increased during the early stages after onset,and their levels were positively correlated with the severity of the disease.The changes of serum OCLN levels were more significant than serum SDC-1levels,and excessive levels of serum OCLN may indicate the poor prognosis of anterior circulation acute cerebral infarction.2.Serum OCLN and SDC-1 levels both had positive correlations with serum MMP-9levels and MMP-9 / TIMP-1,and the correlations of OCLN was stronger,which suggested that MMP-9 and TIMP-1 might participate in the pathological processes that OCLN and SDC-1 were degraded from blood-brain barrier to the peripheral blood circulation.