Role of TXNIP/NLRP3 in sepsis-induced myocardial dysfunction

Myocardial injury is one of the main symptoms of sepsis. However, the mechanisms underlying sepsis-induced myocardial dysfunction remain unclear. In the present study, the concentration of cardiac troponin T (CTnT) in serum was measured using an enzyme-linked immunosorbent assay kit. The levels of interleukin (IL)-1 beta and IL-18 were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and the level of malondialdehyde (MDA) was determined using a corresponding kit. Myocardial pathology was analyzed via hematoxylin and eosin staining. RT-qPCR analysis and western blotting and/or immunohistochemistry were used to quantify the expression levels of thioredoxin-interacting protein (TNXIP), NOD-like receptor pyrin domain containing 3 (NLRP3), cleaved caspase-1, caspase-1, catalase and manganese-superoxide dismutase (MnSOD). The viability of cells was determined using a cell counting kit-8. Apoptosis and reactive oxygen species (ROS) were examined using flow cytometry. Models of sepsis-induced myocardial injury were successfully established; evidence included increases in the levels of CTnT, IL-1 beta, IL-18 and MDA and myocardial tissue damage in vivo, and decreased cell viability and improvements in IL-1 beta and IL-18 in vitro. The levels of TXNIP, NLRP3 and cleaved caspase-1 were upregulated in the sepsis models. Small interfering RNA targeting TNXNIP (siTXNIP) increased cell viability, reduced the apoptotic rate and attenuated the release of IL-1 beta and IL-18. The levels of TXNIP, NLRP3 and cleaved caspase-1 and production of ROS were suppressed by siTXNIP, accompanied by increases in catalase and MnSOD. TXNIP/NLRP3 serves an important role in the development of sepsis-induced myocardial damage.