【作者】 黄娟；

【导师】 袁毅；

【作者基本信息】 中南大学 ， 临床医学（专业学位）， 2025， 硕士

【摘要】 目的:量化急性大血管闭塞缺血性脑卒中(Acute Ischemic Stroke with Large Vessel Occlusion,AIS-LVO)患者血栓的组织病理学和生化成分,同时评估血栓成分与卒中分型、介入参数、影像学特征及临床预后之间的关联,进一步全面了解脑卒中血栓,以期指导卒中病因机制研究及后续二级预防。方法:本研究为多中心、前瞻性队列研究,自2020年1月至2024年10月收集来自中南大学湘雅三医院、长沙市第四医院接受血管内介入治疗的AIS-LVO患者血栓组织标本及临床数据,共纳入168例责任血栓。利用病理染色技术对血栓标本进行组织染色及成分划定,利用Orbit Image Analysis软件量化血栓组织中红细胞(Red Blood Cell,RBC)、白细胞(White Blood Cell,WBC)、纤维蛋白和血小板(Fibrin and Platelet,F+P)、高迁移率族蛋白B1(High Mobility Group Box 1 protein,HMGB1)、中性粒细胞胞外诱捕网(Neutrophil Extracellular Traps,NETs)的丰度,探究不同血栓在组成成分上是否存在差异,同时对血栓各成分含量与卒中病因、介入相关参数、预后等临床数据进行分析。结果:(1)不同病因分组血栓成分存在差异,大动脉粥样硬化(Large Artery Atherosclerosis,LAA)组、心源性栓塞(Cardioembolism,CE)组、不明原因(Stroke of Undetermined Etiology,SUE)组血栓的RBC含量分别为45.40%vs 35.82%vs 33.61%(P=0.004),F+P含量分别为46.25%vs 57.61%vs 58.95%(P<0.001),NETs含量分别为0.76%vs1.78%vs 1.93%(P=0.02)。CE血栓和SUE血栓各种血栓成分未见显著统计学差异。(2)大脑中动脉高密度征在富RBC血栓中较富F+P血栓及混合血栓更为常见(90.9%vs 60%vs 16.7%,P<0.001)。大脑中动脉高密度征阳性的血栓中RBC含量较阴性组更高(51.35%vs26.47%,P<0.001),F+P含量较阴性组更低(41.52%vs 65.98%,P<0.001),存在显著统计学差异。(3)再通时间≥60min组血栓中HMGB1中位含量高于再通时间<60min组(10.09%vs 11.82%,P=0.038)。总取栓次数与血栓中NETs含量呈正相关(r=0.194,P=0.012,n=168),首次取栓后m TICI分级(0,1,2a,2b,3级)与血栓中NETs含量呈负相关(r=-0.279,P=0.002,n=168),手术结束后m TICI分级与血栓中NETs含量呈负相关(r=-0.230,P=0.003,n=168),与RBC、WBC、F+P、HMGB1含量未见相关性。(4)良好再通组血栓中RBC含量显著高于不良再通组(40.23%vs 28.65%,P=0.005),F+P含量(52.64%vs62.64%,P=0.015)、NETs含量(1.11%vs 7.28%,P=0.004)显著低于不良再通组。(5)预后不良组患者血栓中NETs含量(1.80%vs 0.90%,P=0.045)、HMGB1(11.10%vs 9.63%,P=0.018)含量显著高于预后良好组,差异具有统计学意义。结论:(1)不同病因分组血栓成分存在异质性,LAA组血栓含有更高的RBC及更低的F+P及NETs含量,CE组血栓和SUE组血栓各成分比例相似,提示不明原因型卒中有来源于心源性卒中可能。(2)血栓中高RBC含量、低F+P及低NETs含量与良好再通相关,而高HMGB1含量更易导致再通时间≥60min,高NETs含量与更多的取栓次数及更差的术后m TICI分级相关,可能与取栓抵抗相关。(3)血栓中高RBC含量、低F+P含量与大脑中动脉高密度征相关。(4)NETs和HMGB1是血栓的重要组成部分,血栓中高NETs及HMGB1含量与不良功能预后相关。图8幅,表10个,参考文献94篇更多还原

【Abstract】 Objective:To quantify the histopathologic and biochemical composition of thrombus in patients with acute large vessel occlusion ischemic stroke,and to assess the association between thrombus composition and stroke classification,interventional parameters,imaging features,and clinical prognosis,in order to further develop a comprehensive understanding of stroke thrombus,with a view to guiding the study of stroke etiology and subsequent secondary prevention.Method:This study was a multicenter,prospective cohort study that collected thrombus tissue specimens,clinical data,and procedural parameters from patients with AIS-LVO undergoing endovascular interventions at the Third Xiangya Hospital of Central South University and the Fourth Hospital of Changsha from January 2020 to October 2024,and a total of 168 responsible thrombi were included.Pathological staining techniques,including HE staining and immunohistochemical staining,were used for tissue staining and delineation of the components of thrombus specimens,and Orbit Image Analysis software was used to quantify the abundance of erythrocytes,leukocytes,fibrin and platelets,HMGB1,and NETs in the thrombus tissues,to explore whether there was any difference between different thrombi in terms of their compositional components,and at the same time,to compare the content of the various components of thrombus with that of stroke The content of each thrombus component was also analyzed in relation to clinical data on stroke etiology,reperfusion therapy,and prognosis.Results:(1)There were differences in thrombus composition among different etiologic subgroups,the RBC content of thrombus in LAA group,CE group and SUE group were 45.40%vs 35.82%vs 33.61%(P=0.004),F+P content was 46.25%vs 57.61%vs 58.95%(P<0.001),NETs content were 0.76%vs 1.78%vs 1.93%(P=0.02).No statistically significant difference was seen in the various thrombus components of CE thrombus and SUE thrombus.(2)Middle cerebral artery hyperdensity sign were more common in RBC-rich thrombi than F+P-rich thrombi and mixed thrombi(90.9%vs.60%vs.16.7%),and RBC-rich thrombi were highly correlated(P<0.001).Thrombi positive for middle cerebral artery hyperdensity sign had higher RBC content(51.35%vs.26.47%,P<0.001)and lower F+P content(41.52%vs.65.98%,P<0.001)than those negative,which were statistically significant differences.(3)The median levels of HMGB1 in thrombi were higher in the group with recanalization time≥60 min than in the group with recanalization time<60 min(10.09%vs 11.82%,P=0.038).The total number of thrombus retrieval was positively correlated with NETs content in thrombus(r=0.194,P=0.012,n=168),m TICI grading after the first retrieval of thrombus(grades 0,1,2a,2b,3)was negatively correlated with NETs content in thrombus(r=-0.279,P=0.002,n=168),and after the end of the procedure m TICI grading was negatively correlated with NETs content in thrombus was negatively correlated(r=-0.230,P=0.003,n=168),and no correlation were seen with RBC,WBC,F+P,and HMGB1 content.(4)The RBC content of thrombus in the good recanalization group was significantly higher than that in the poor recanalization group(40.23%vs 28.65%,P=0.005),and the F+P content(52.64%vs 62.64%,P=0.015)and NETs content(1.11%vs 7.28%,P=0.004)were significantly lower than that in the poor recanalization group.(5)The levels of NETs(1.80%vs 0.90%,P=0.045)and HMGB1(11.10%vs 9.63%,P=0.018)in thrombus of patients in the poor prognosis group were significantly higher than those in the good prognosis group.Conclusion:(1)The heterogeneity of thrombus composition among different etiologic groups,with higher RBC content and lower F+P and NETs content ratios in the LAA group,and similarity in thrombus composition among CE and SUE thrombi,support the possibility that stroke of unknown origin may have originated part from a cardiac stroke source.(2)High RBC content,low F+P,and low NETs content in thrombi were associated with first-pass recanalization and good recanalization,whereas high HMGB1 content was more likely to result in recanalization times≥60 min,and high NETs content was associated with more thrombus retrievals and poorer postprocedural m TICI grades,which may be related to resistance to thrombus retrieval.(3)High RBC content and low F+P content in the thrombus were associated with the middle cerebral artery hyperdensity sign.(4)NETs and HMGB1 are important components of thrombus,and high NETs and HMGB1 content in thrombus is associated with poor functional prognosis.更多还原