Relationship Between ZO-1/OCLN Expression And Development Of Perihematoma Edema After Spontaneous Intracerebral Hemorrhage

Objective: Perihematomal edema(PHE)is a key factor of poor prognosis in intracerebral hemorrhage(ICH)patients with an unclear mechanism of occurrence.It has been reported that blood brain barrier(BBB)damage is involved in its pathogenesis.The levels of zonula occludens-1(ZO-1)and occludin(OCLN)in peripheral mononuclear cells,which are tight junction protein and closed protein of BBB,can directly reflect the extent of BBB damage.Therefore,this study intends to explore the relationship between expression of ZO-1,OCLN and development of PHE to provide a theoretical basis of early clinical intervention of PHE effectively and improvement of patient prognosis.Methods: In strict accordance with the inclusion and exclusion criteria,ICH patients were hospitalized from September 1,2020 to August 31,2021 who were selected as the participants.ICH patients were collected peripheral venous blood and neuroimaging data at 1,3,7 and 14 days after onset.The expression levels of ZO-1 and OCLN in mononuclear cells were tested by Western Blot(WB)and quantitative real time polymerase chain reaction(qRT-PCR);Focal indicators of ICH patients were analyzed on the 3D Slicer imaging analysis software platform: RPHE(relative PHE)which was the best index reflecting relationship of PHE and hematoma,EED(edema extentension distance)which was the best index reflecting development of PHE via inflammation,and SH(sphericity of hematoma)which was an original morphological index of hematoma.Analysis of variance(ANOVA),correlation analysis were performed by IBM SPSS Statistics,Sigma Stat and Graph Pad Prism software.Two-sided P <0.05 was defined as the statistical significance.Results: 68 patients with ICH participated in this study.on 3 days after onset of ICH,The lowest expression levels of ZO-1 and OCLN were reached(F≥7.222,P≤0.012);RPHE,EED,and SH reached the highest values(F≥29.144,P<0.001).At this time point,ZO-1 and OCLN expression were positively correlated to each other(r≥0.775,P<0.001);all the indicators reflecting the development of PHE were positively correlated with each other(r≥0.776,P≤0.001);both of RPHE and SH were negatively correlated with ZO-1 and OCLN expression(r≤-0.557,P≤0.049),while EED was only negatively correlated with OCLN expression(r≤-0.781,P≤0.003).Conclusion: On the 3 day after the onset of ICH,the gene expression of ZO-1/OCLN of mononuclear cells in the peripheral venous blood and PHE reached the lowest and highest values respectively.At this time point,SH,as the original morphological index of hematoma lesion,was a related factor of PHE development.