Breviscapine inhibits the formation and mechanism of intracranial aneurysms by regulating the Nrf2 pathway
10.19405/j.cnki.issn1000-1492.2022.04.014
- Author:
Qiyuan Ai
1
;
Yong Wang
1
;
Ruichun Xu
1
;
Zhen Peng
1
;
Jinsong Li
1
Author Information
1. Dept of Neurosurgery，The Third Affiliated Hospital of Guizhou Medical University，Duyun 558000
- Publication Type:Journal Article
- Keywords:
intracranial aneurysm;
breviscapine;
α-smooth muscle actin;
nuclear factor erythroid 2 related factor 2;
vascular smooth muscle cells
- From:
Acta Universitatis Medicinalis Anhui
2022;57(4):579-585
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effect and mechanism of breviscapine(Bre) on the formation of intracranial aneurysm(IA) and its influence on nuclear factor erythroid 2-related factor 2(Nrf2) pathway in a rat model.
Methods:The rat model of IA was established by elastase injection. The rats were randomly divided into Sham group, Model group and Bre group with 15 rats in each group. The Bre group was intraperitoneally injected with 50 mg/kg Bre every day, the Sham group and Model group were intraperitoneally injected with the same volume of normal saline for 3 weeks. During this period, the incidence of IA, survival rate and systolic blood pressure were recorded, immunofluorescence staining and qRT-PCR were employed to assay the expression of α-smooth muscle actin(α-SMA) and smooth muscle 22α(SM22α). Hydrogen peroxide(H2O2, 0.5 mmol/L) was used to treat rat vascular smooth muscle cells(VSMC) to induce oxidative damage, and then co-incubated with Bre(100 μmol/L) or/and ML385(Nrf2 inhibitor), Western blot, qRT-PCR, ELISA, DCFH-DA fluorescence staining and flow cytometry were used to detect the expression of Nrf2, contractile phenotype-related protein and inflammatory cytokine, reactive oxygen species(ROS) production and cell apoptosis rate, respectively.
Results:In IA rats, Bre treatment up-regulated the expression of nuclear Nrf2, improved the pathological changes of IA, reduced the incidence of IA, improved the survival rate, and lowered the systolic blood pressure. In VSMC treated with H2O2, Bre pretreatment increased the expression of Nrf2, antioxidant enzymes, α-SMA and SM22α, reduced the expression of matrix metalloproteinases(MMP)-2 and MMP-9, the production of ROS and cell apoptosis, and reduced inflammation in cerebral arteries cell infiltration and expression of pro-inflammatory cytokines. Inhibition of Nrf2 weakened the therapeutic effect of Bre pretreatment in H2O2treated VSMC.
Conclusion:Bre can effectively reduce the oxidative stress and inflammation in VSMC, thereby reducing the formation and rupture of IA in rat. The mechanism may be related to the activation of the Nrf2 pathway.
- Full text:2025021809423329045灯盏花素通过调节Nrf2途...大鼠颅内动脉瘤的形成和机制_艾奇渊.pdf
