Protection against post-resuscitation renal injury by Artesunate via inhibition of caspase-3/Gasdermin E -mediated pyroptosis.

Background: Post-resuscitation renal injury is the common complication after cardiac arrest and resuscitation. Artesunate (Art) has been confirmed to protect against regional ischemia-reperfusion injuries in multiple organs. This study aimed to determine the effects of Art on post-resuscitation renal injury and clarify whether the mechanism is related to inhibition of the caspase-3/Gasdermin E pyroptosis pathway. Methods: Twenty-two swine were divided into a Sham, Cardiopulmonary resuscitation (CPR), and CPR + Art groups. Blood samples were collected to measure serum creatinine and blood urea nitrogen levels. Samples of renal tissue were obtained for histopathological assessment of injury, the apoptosis index, contents of proinflammatory cytokines, kidney injury molecule-1, neutrophil gelatinase-associated lipid carrier, and pyroptosis-related protein expression levels. Results: Compared with the Sham group, the biomarkers of renal injury were significantly increased in the CPR and CPR + Art groups. Levels of these biomarkers were significantly lower in the CPR + Art group than in the CPR group. Renal pathological damage and cell apoptosis were observed in the CPR and CPR + Art groups after resuscitation and were markedly less severe in the CPR + Art group. The expression levels of caspase-3/Gasdermin E pyroptosis related proteins and proinflammatory cytokines were significantly increased in the CPR and CPR + Art groups compared with the Sham group. Treatment with Art significantly decreased the expression of these indicators of cell pyroptosis. Conclusions: Art treatment could alleviate post-resuscitation renal injury, and its mechanism may be related to the inhibition of caspase-3/Gasdermin E pyroptosis pathway.