Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17

European Journal of Medical Research

Qiancheng Luo¹  Qi Kang¹  Lei Xu¹  Min Hang¹  Dongfeng Guo¹  Guorong Liu¹  Guo Chen¹  Qinqin Jin¹  Rui Liu²  Kaili Qu³ 

[1] Department of Critical Care Medicine, Shanghai Gongli Hospital, The Second Military Medical University, 200135, Shanghai, People’s Republic of China;Department of Endocrinology, Shanghai Gongli Hospital, The Second Military Medical University, 200135, Shanghai, People’s Republic of China;Postgraduate Training Base in Shanghai Gongli Hospital, Ningxia Medical University, 200135, Shanghai, People’s Republic of China;

关键词: Sepsis;    Inflammation;    Cangrelor;    Platelet;    GPR17;   

DOI  :  10.1186/s40001-021-00536-4

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY