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Updated: Nov 24, 2025
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Ticagrelor alleviates sepsis-induced myocardial injury via an adenosine-dependent pathway in a mouse sepsis model
Shengxing Tang1, Cong Fu2, Qiancheng Xu3
1Department of Cardiology, Yi Ji Shan Hospital affiliated to Wan Nan Medical College, Wuhu, China.
Purpose:
The purpose of this study was to determine whether ticagrelor, a classic anti-platelet drug, has a therapeutic effect on sepsis-induced myocardial injury.
Methods:
The C57BL6J mice received oral ticagrelor (10, 25 and 50 mg/kg) for seven days after which cecum ligation and puncture (CLP) were performed. An adenosine-receptor antagonist (CGS15943) was administered two hours before CLP. After 24 h, cardiac function was measured using cardiac echocardiography, then the heart and blood were collected. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL staining) were used to observe pathological changes and cardiomyocyte apoptosis. Plasma concentration of TNF-α, IL-6 and adenosine and myocardial tissue levels of TNF-α and IL-6 were determined. Survival analysis was performed. Western blot was used to determine the expression of a signalling protein in the myocardial tissue.
Results:
The HE and TUNEL staining showed less inflammatory cell infiltration and less cardiomyocyte apoptosis in the ticagrelor group. Cardiac echocardiography showed preserved heart function in the ticagrelor group. Plasma TNF-α, IL-6 and relative expression of TNF-α and IL-6 in myocardial tissue were significantly lower in the ticagrelor group. Plasma adenosine levels were significantly higher in the ticagrelor group. Adenosine-receptor antagonists significantly blocked the protective effect of ticagrelor. Ticagrelor reduced the mortality of sepsis mice, and this reduction was blocked by the adenosine-receptor antagonist. Western blot showed that ticagrelor activated the phosphorylation of AKT and mTOR. Adenosine-receptor antagonists inhibited the activation of AKT and mTOR.
Conclusion:
The protective effect of ticagrelor was dependent on adenosine-receptor activation, with downstream upregulation of phosphorylation of AKT and mTOR.
Insights
Ticagrelor, an anti-platelet drug, protects against sepsis-induced myocardial injury by activating adenosine receptors and the AKT/mTOR pathway, reducing inflammation and improving survival in mice.
Area of Science:
- Cardiology
- Pharmacology
- Sepsis Research
Background:
- Sepsis-induced myocardial injury is a serious complication with high mortality.
- Current treatments for sepsis-induced myocardial injury are limited.
- Ticagrelor is a P2Y12 inhibitor with anti-platelet effects.
Purpose of the Study:
- To investigate the therapeutic effect of ticagrelor on sepsis-induced myocardial injury.
- To explore the underlying mechanism of ticagrelor's protective effects.
Main Methods:
- C57BL6J mice underwent cecum ligation and puncture (CLP) to induce sepsis.
- Mice were treated with ticagrelor and/or an adenosine-receptor antagonist.
- Cardiac function, cardiomyocyte apoptosis, inflammatory markers, and signaling pathways (AKT/mTOR) were assessed.
Main Results:
- Ticagrelor treatment preserved cardiac function and reduced cardiomyocyte apoptosis and inflammation.
- Ticagrelor increased plasma adenosine levels and activated AKT/mTOR phosphorylation.
- The protective effects of ticagrelor were blocked by an adenosine-receptor antagonist.
Conclusions:
- Ticagrelor exerts a protective effect against sepsis-induced myocardial injury.
- This effect is mediated through adenosine-receptor activation and subsequent AKT/mTOR pathway phosphorylation.
- Ticagrelor demonstrates potential as a therapeutic agent for sepsis-induced myocardial injury.
