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- Title
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.
- Authors
张俊; 王巍; 王帮奎; 曾杰
- Abstract
Objective To investigate the mechanism of ADAMTS-5 in accelerating the formation of neutro‑ phil 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, neutro‑ phil 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 IHCMPO 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.
- Publication
Journal of Practical Medicine / Shiyong Yixue Zazhi, 2023, Vol 39, Issue 19, p2469
- ISSN
1006-5725
- Publication type
Article
- DOI
10.3969/j.issn.1006-5725.2023.19.010