Ulinastatin protects against sepsis-induced myocardial injury by inhibiting NLRP3 inflammasome activation

Myocardial injury is the primary manifestation of multiple organ dysfunction during sepsis, however, the mechanisms underlying sepsis-induced myocardial injury remain unclear. Similarly, no effective therapeutics have yet been developed for myocardial injury. In the present study, the role of the NOD-like receptor 3 (NLRP3) inflammasome on cardiac function were characterized and the effects of different ulinastatin (UTI) doses in protecting a septic rat model from myocardial injury were elucidated. To evaluate UTI efficacy on cardiac function, its effects on anti-inflammatory mediators were analyzed and its cardioprotective effects were investigated. It was demonstrated that circulatory levels of tumor necrosis factor-α and interleukin-1β were elevated during sepsis. It was also observed that NLRP3 and caspase-1 expression enhanced post-cecal ligation and puncture (CLP), and that high UTI levels protected against myocardial injury induced by sepsis. To the best of our knowledge, this is the first study to demonstrate that the mechanisms underpinning UTI-mediated myocardial protection were due to the downregulation of the NLRP3/caspase-1/IL-1β signaling pathway. Based on these findings, it is proposed that UTI exerts beneficial effects during sepsis-induced myocardial injury.