Tianxiang Pills Alleviates Myocardial Cell Pyroptosis in Rat Model of Myocardial Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress via ROS/Caspase-1/GSDMD Signaling Pathway
10.13422/j.cnki.syfjx.20260101
- VernacularTitle:天香丹通过调控ROS/Caspase-1/GSDMD信号通路抑制氧化应激减轻心肌缺血再灌注大鼠心肌细胞焦亡的机制
- Author:
Fei ZENG
1
;
Hao HUANG
1
;
Yu CAO
1
;
Yaoming XI
1
;
Jing LUO
1
Author Information
1. Traditional Chinese Medicine Inheritance and Innovation Center， The Fourth Affiliated Hospital of Xinjiang Medical University， Urumqi 830000，China
- Publication Type:Journal Article
- Keywords:
Tianxiang pills;
reactive oxygen species/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D signaling pathway;
myocardial ischemia/reperfusion injury;
rat;
pyroptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(18):143-150
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanism by which Tianxiang pills （TXP） alleviates myocardial cell pyroptosis in the rat model of myocardial ischemia/reperfusion （I/R） injury through modulating the reactive oxygen species （ROS）/cysteinyl aspartate-specific proteinase-1 （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsA total of 54 SPF-grade adult male Sprague-Dawley rats were randomized into six groups （n=9）： sham （thoracotomy only without ligation）， I/R （left anterior descending coronary artery ligation for 30 min followed by reperfusion）， NAC （positive control， N-acetylcysteine， 150 mg·kg-1， by gavage）， low-dose Tianxiang pills （TXP-L， 2.5 g·kg-1， by gavage）］， medium-dose Tianxiang pills （TXP-M， 5 g·kg-1， by gavage）， and high-dose Tianxiang pills （TXP-H， 10 g·kg-1， by gavage）. The fluorescent probe method was employed to measure the ROS level. Biochemical assay kits were employed to determine the Caspase-1 activity， superoxide dismutase （SOD） activity， malondialdehyde （MDA） content， and glutathione peroxidase （GSH-Px） activity. Myocardial infarct size was assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Western blot analysis was performed to evaluate the expression levels of proteins in the ROS/Caspase-1/GSDMD pathway， including GSDMD， cleaved Caspase-1/Caspase-1 ratio， the N-terminal domain of GSDMD （GSDMD-N）， and the p22-phox subunit of the reduced nicotinamide adenine dinucleotide phosphate （NADPH） oxidase complex. Enzyme-linked immunosorbent assay （ELISA） was utilized to determine the concentration of interleukin-1β （IL-1β）. Transmission electron microscopy （TEM） was employed to observe mitochondrial structure and to score the degree of mitochondrial swelling. ResultsCompared with the Sham group， the I/R group exhibited elevated the levels of ROS， Caspase-1 activity， GSDMD expression， IL-1β concentration， MDA content， infarct area， mitochondrial swelling score， cleaved Caspase-1/Caspase-1， GSDMD-N， and p22phox and decreased activities of SOD and GSH-Px （P<0.05）. Compared with the I/R group， NAC and different doses of TXP significantly reduced the ROS level， Caspase-1 activity， GSDMD expression， IL-1β concentration， MDA content， infarct area， and mitochondrial swelling score. Moreover， they downregulated the expression of cleaved Caspase-1/Caspase-1， GSDMD-N， and p22phox and increased the activities of SOD and GSH-Px （P<0.05）. Furthermore， TXP exerted effects on ROS， MDA， SOD， GSH-Px， Caspase-1 activity， GSDMD expression， IL-1β concentration， cleaved Caspase-1/Caspase-1， GSDMD-N， p22phox， infarct area， and mitochondrial swelling score in a dose-dependent manner （P<0.05）. ConclusionTianxiang pills alleviates myocardial I/R injury by mitigating oxidative stress and cell pyroptosis through the inhibition of the ROS/Caspase-1/GSDMD signaling pathway.
