Artemisinin attenuated ischemic stroke induced pyroptosis by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway - 23/07/24
Abstract |
Background |
To explore the neuroprotective mechanism of artemisinin against ischemic stroke from the perspective of NLRP3-mediated pyroptosis.
Methods |
Serum metabolomics technology was used to analyze the serum samples of mice, and KEGG metabolic pathway was analyzed for the different metabolites in the samples. PIT model and OGD/R model were used to simulate ischemic stroke damage in vivo and in vitro. Hoechst 33342 staining, Annexin V-FITC/PI staining and TUNEL staining were used to detect the pyroptosis rate of cells. The contents of IL-1β and IL-18 in PC12 cells and serum of mice were detected by ELISA. The expressions of NLRP3, ASC-1, Caspase-1 and TXNIP in PC12 cells and mouse brain tissue were detected by Western Blot.
Results |
Serum metabolic profiles of animal models identified 234 different metabolites and 91 metabolic pathways. Compared with the Sham group and the Stroke+ART group, the KEGG pathway in the Stroke group was concentrated in the Necroptosis pathway associated with cell growth and death, and the NLRP3 inflammasome-mediated pyroptosis pathway was activated in the Necroptosis pathway after ischemic stroke. The results of in vivo and in vitro experiments showed that pretreatment with 10 μM artemisinin reduced ROS production, decreased Δψm, reduced pyroptosis, maintained neuronal cell morphology, and down-regulated the contents of IL-1β and IL-18 as well as the expression of key proteins of NLRP3, ASC-1, Caspase-1 and TXNIP(p<0.01).
Conclusion |
Artemisinin can reduce neuronal pyroptosis induced by ischemic stroke by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | The NLRP3 inflammasome-mediated pyroptosis pathway was activated after ischemic stroke. |
• | ART alleviates mitochondrial damage by inhibiting the abnormal production of ROS and maintaining the stability of Δψm. |
• | ART blocks the assembly of NLRP3 inflammasomes by inhibiting the ROS, further inhibiting cell pyroptosis. |
Abbreviations : ART, ASC-1, Caspase-1, IL-18, IL-1β, IS, NLRP3, OGD/R, PIT, ROS, T-PA, TXNIP, Δψm
Keywords : Metabonomics, Artemisinin, PIT, OGD/R, NLRP3 inflammasome, MCC950, Pyroptosis
Plan
Vol 177
Article 116894- août 2024 Retour au numéro
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