Protection of beta-blocker and 5-hydroxytryptamine 1A receptor agonist on myocardial ischemia injury in rats by regulating the NLRP3/Caspase-1/GSDMD pathway
- 1Department of Psycho-cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
Abstract
Objective: To explore the effects and related mechanisms of a β-blocker combined with a 5-hydroxytryptamine 1A receptor (5-HT1AR) agonist on MI injuries in rats. Methods: TTC/Evans blue, H&E, Masson, and TUNEL staining were used to assess infarction area, pathological damage, fibrosis, and apoptosis in myocardial tissue. The ELISA kits were used to detect IL-1β and IL-18 levels. The immunohistochemical (IHC) staining was used in conjunction with qRT-PCR and Western blot to determine IL-1β, IL-18, NLRP3, pro Caspase-1, cleaved Caspase-1, GSDMD-FL, and GSDMD-N expression levels. Results: In myocardial tissue, the β-blocker combined with the 5-HT1AR agonist effectively reduced infarction size, mitigated pathological injury, alleviated fibrosis, and prevented apoptosis. Meanwhile, the β-blocker combined with the 5-HT1AR agonist downregulated IL-1β and IL-18 levels in serum and myocardial tissue. Notably, although it barely altered the expression of the pyroptosis precursor proteins pro Caspase‑1 and GSDMD‑FL, the combined therapy strongly suppressed the mRNA and protein levels of NLRP3, cleaved Caspase‑1, and GSDMD‑N, and reduced the ratios of pro Caspase‑1/cleaved Caspase‑1 and GSDMD-FL/GSDMD-N in myocardial tissue. Conclusion: β-blocker combined with the 5-HT1AR agonist relieves MI injuries by suppressing the NLRP3/Caspase-1/GSDMD pathway.
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BibTeX
@article{chen2026protection,
title = {{Protection of beta-blocker and 5-hydroxytryptamine 1A receptor agonist on myocardial ischemia injury in rats by regulating the NLRP3/Caspase-1/GSDMD pathway}},
author = {Haiyang Chen and Yanwei Li and Meiyan Liu and Yunpeng Chi and Lijun Zhang},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360695},
url = {https://doi.org/10.1371/journal.pone.0360695},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Protection of beta-blocker and 5-hydroxytryptamine 1A receptor agonist on myocardial ischemia injury in rats by regulating the NLRP3/Caspase-1/GSDMD pathway
AU - Haiyang Chen
AU - Yanwei Li
AU - Meiyan Liu
AU - Yunpeng Chi
AU - Lijun Zhang
PY - 2026
DA - 2026/10/14
JO - PLOS One
DO - 10.1371/journal.pone.0360695
UR - https://doi.org/10.1371/journal.pone.0360695
AB - Objective: To explore the effects and related mechanisms of a β-blocker combined with a 5-hydroxytryptamine 1A receptor (5-HT1AR) agonist on MI injuries in rats. Methods: TTC/Evans blue, H&E, Masson, and TUNEL staining were used to assess infarction area, pathological damage, fibrosis, and apoptosis in myocardial tissue. The ELISA kits were used to detect IL-1β and IL-18 levels. The immunohistochemical (IHC) staining was used in conjunction with qRT-PCR and Western blot to determine IL-1β, IL-18, NLRP3, pro Caspase-1, cleaved Caspase-1, GSDMD-FL, and GSDMD-N expression levels. Results: In myocardial tissue, the β-blocker combined with the 5-HT1AR agonist effectively reduced infarction size, mitigated pathological injury, alleviated fibrosis, and prevented apoptosis. Meanwhile, the β-blocker combined with the 5-HT1AR agonist downregulated IL-1β and IL-18 levels in serum and myocardial tissue. Notably, although it barely altered the expression of the pyroptosis precursor proteins pro Caspase‑1 and GSDMD‑FL, the combined therapy strongly suppressed the mRNA and protein levels of NLRP3, cleaved Caspase‑1, and GSDMD‑N, and reduced the ratios of pro Caspase‑1/cleaved Caspase‑1 and GSDMD-FL/GSDMD-N in myocardial tissue. Conclusion: β-blocker combined with the 5-HT1AR agonist relieves MI injuries by suppressing the NLRP3/Caspase-1/GSDMD pathway.
SN - 1932-6203
ER -