ADAMTS-5在加速形成中性粒细胞胞外陷阱恶化颅内动脉瘤疾病进展中的作用机制

doi:10.3969/j.issn.1006-5725.2023.19.010

Abstract

Abstract:

Objective To investigate the mechanism of ADAMTS-5 in accelerating the formation of neutrophil extracellular traps （NETs） and worsening the progression of intracranial aneurysm （IA）. Methods IA mouse model was constructed. Adenovirus-mediated overexpression or knockdown ADAMTS-5 in arterial wall of the circle of Willis in the right cisterna of mice brain was conducted. Sixty mice were randomly divided into six groups of sham group， model group， shRNA-NT group， shRNA-ADAMTS-5 group， OE-vector group and OE-ADAMTS-5 group， with ten mice in each. H&E staining was used to analyze the infiltration of immune cells in arterial wall of the circle of Willis； and immunohistochemistry （IHC） to detect the expression of neutrophil markers MPO， neutrophil extracellular trap （NETs） markers H3Cit and ADAMTS-5 protein expression level in arterial wall of the circle of Willis. qPCR and western blot were used to analyze the expression of ADAMTS-5 mRNA and protein in arterial wall of the circle of Willis in sham group and model group. The expression of MPO， H3Cit， ADAMTS-5 and Collagen Ⅳ in arterial wall of the circle of Willis was detected by western blot. Results H&E staining showed that there were a large number of immune cells infiltrated in arterial wall of the circle of Willis in the model group， and IHC-MPO staining， IHC-H3Cit staining and IHC-ADAMTS-5 staining showed a large number of neutrophils infiltrated and NETs formed. ADAMTS-5 staining positive area overlapped with H3Cit staining positive area. Compared with that in the sham group， the expression of ADAMTS-5 mRNA and protein was higher in the model group （P < 0.05）. Compared with the model group， knocking down/ overexpression ADAMTS-5 in arterial wall of the circle of Willis decreased/increased NETs formation （P < 0.05）. Conclusion ADAMTS-5 plays an important role in driving formation of NETs and promoting disease progression of IA in mouse models.

Key words: intracranial aneurysms, neutrophil extracellular traps, ADAMTS-5

CLC Number:

R739.41

Jun ZHANG,Wei WANG,Bangkui WANG,Jie. ZENG. Mechanism of ADAMTS⁃5 in accelerating formation of neutrophil extracellular traps and worsening progression of intracranial aneurysm[J]. The Journal of Practical Medicine, 2023, 39(19): 2469-2474.

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References 19

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Mechanism of ADAMTS⁃5 in accelerating formation of neutrophil extracellular traps and worsening progression of intracranial aneurysm

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