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S100β、基质金属蛋白酶-9、D-二聚体和热休克蛋白70是短暂性大脑中动脉闭塞小鼠模型急性脑梗死的血清生物标志物。

S100ß, Matrix Metalloproteinase-9, D-dimer, and Heat Shock Protein 70 Are Serologic Biomarkers of Acute Cerebral Infarction in a Mouse Model of Transient MCA Occlusion.

作者信息

Choi Jong-Il, Ha Sung-Kon, Lim Dong-Jun, Kim Sang-Dae, Kim Se-Hoon

机构信息

Department of Neurosurgery, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.

Department of Neurosurgery, Korea University Medical Center, Seoul, Korea.

出版信息

J Korean Neurosurg Soc. 2018 Sep;61(5):548-558. doi: 10.3340/jkns.2017.0200. Epub 2018 May 4.

DOI:10.3340/jkns.2017.0200
PMID:29724092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6129755/
Abstract

OBJECTIVE

Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether S100β, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction.

METHODS

Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma S100β, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay.

RESULTS

The average infarction volume was 12.32±2.31 mm3 and 46.9±7.43 mm3 in the 30- and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was 1.6±0.55 and 3.2±0.70, respectively. S100β, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, S100β and MMP-9 expressions correlated with infarction volumes (p<0.001) and neurological deficits (p<0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and S100β (AUC=0.98).

CONCLUSION

S100β, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

摘要

目的

诊断急性脑梗死对于确定中风患者的预后至关重要。尽管有许多用于快速诊断的血清学检测方法,但血清学检测目前在临床中的应用有限。我们研究了S100β、基质金属蛋白酶-9(MMP-9)、D-二聚体和热休克蛋白70(HSP70)是否可作为急性脑梗死的生物标志物。

方法

采用改良的腔内丝线技术诱导局灶性脑缺血。将小鼠随机分为30分钟闭塞组(n = 10)、60分钟闭塞组(n = 10)或假手术组(n = 5)。4小时后,评估神经功能缺损并采集血样。计算梗死体积,并使用酶联免疫吸附测定法测量血浆S100β、MMP-9、D-二聚体和HSP70水平。

结果

30分钟和60分钟组的平均梗死体积分别为12.32±2.31mm³和46.9±7.43mm³。两个缺血组的平均神经功能评分别为1.6±0.55和3.2±0.70。缺血4小时后,S100β、MMP-9和HSP70表达显著增加(p = 0.001)。此外,S100β和MMP-9表达与梗死体积(p < 0.001)和神经功能缺损(p < 0.001)相关。各组间D-二聚体表达无显著差异(p = 0.843)。受试者工作特征曲线(AUC)下面积显示MMP-9、HSP70(AUC = 1)和S100β(AUC = 0.98)具有高敏感性和特异性。

结论

S100β、MMP-9和HSP70可补充当前评估脑梗死的诊断工具,表明它们可作为急性脑梗死的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/06b587c35357/jkns-2017-0200f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/d06716f73a74/jkns-2017-0200f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/c934b3d8b434/jkns-2017-0200f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/b9c9308116b3/jkns-2017-0200f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/2a05803333bc/jkns-2017-0200f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/58a7fb35e09b/jkns-2017-0200f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/72af3abe1909/jkns-2017-0200f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/06b587c35357/jkns-2017-0200f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/d06716f73a74/jkns-2017-0200f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/c934b3d8b434/jkns-2017-0200f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/b9c9308116b3/jkns-2017-0200f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/2a05803333bc/jkns-2017-0200f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/58a7fb35e09b/jkns-2017-0200f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/72af3abe1909/jkns-2017-0200f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/995f/6129755/06b587c35357/jkns-2017-0200f7.jpg

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