Abstract
BackgroundSepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug.MethodsIn our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models.ResultsTdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1β (p < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001).ConclusionOur study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.
Highlights
Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate
Treating with 5 mg/kg cangrelor did not enhance the survival rate compared with cecal ligation and double puncture (CLP) group, while treating with 20 mg/kg cangrelor significantly improved the survival rate compared with CLP group (p < 0.001)
In our research, we demonstrated that cangrelor alleviated CLP-induced lung injury in abdominal sepsis by regulating platelet aggregation and the inflammatory response
Summary
Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. Sepsis is a serious disease and will lead a high mortality rate of approximately 22% in all over the world [1]. It has several features like out of controlled inflammatory response, coagulation disorder, and immune dysfunctions [2]. Drugs that effectively improve the treatment of sepsis remain to be developed. Antibiotics are the key method for clinical treatment, but the death rate of sepsis still reaches an astonishing number of 30–40% [9]
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