Ticagrelor alleviates pyroptosis in myocardial ischemia reperfusion-induced acute lung injury

Abstract Background: Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is unknown. Myocardial ischemia-reperfusion injury (MIRI) was shown to induce acute lung injury (ALI) related to pulmonary infection and inflammation. Whether MIRI induces pyroptosis in the lungs remains unclear. Method: Sprague-Dawley rats were randomly divided into four groups: control, MIRI, low ticagrelor (30 mg/kg), and high ticagrelor (100 mg/kg). Rats were treated with ticagrelor or saline via intragastric gavage before undergoing surgery. Serum parameters of CK-MB and LDH were measured using automatic biochemistry analyzers. HE staining to obtain HE scores was performed following the calculation of the wet-to-dry ratio. NLRP3, ASC, and cleaved caspase-1 in lung tissue were detected by western blot, and IL-1β was assessed by ELISA. Immunohistochemistry was used to determine the MPO+, NLRP3+, and cleaved caspase-1+ area. Results: The HE score, wet-to-dry ratio, and MPO+ area were increased in the MIRI group, and attenuated after ticagrelor treatment. Pyroptosis-associated proteins including NLRP3, ASC, and cleaved caspase-1 were elevated in MIRI, and eliminated by ticagrelor. Similar results were observed using immunohistochemistry assays. Conclusions: Pyroptosis was augmented in lung tissue after MIRI, and pre-treatment with ticagrelor attenuated these effects.