Study on the Mechanism of NLRP3/IL-1/ NF-κB Signaling Pathway and Macrophage Polarization in the Occurrence and Development of VTE

The role of inflammation in venous thromboembolism (VTE) has been the focus of recent research. The NLRP3/IL-1/NF-κB signaling pathway and cytokines such as IL-1, regulated by macrophage polarization, may be the key indicators of a prethrombotic state; however, the mechanisms by which they affect the occurrence of VTE remain unclear.We used neurobiological clamps to stimulate the vein wall to induce vascular endothelial damage to generate a rat model of VTE, applied enzyme-linked immunosorbent assay and real time-polymerase chain reaction technology to identify key proteins (IL1β, Caspase-1, NLRP3, and NF-κB P65), gene mRNA levels and protein expression levels of the NLRP3/IL-1/NF-κB signaling pathway in each group of Sprague Dawley rats, and observed the polarization state of M1 (CD86) and M2 (CD206) macrophages using immunohistochemistry.A dark red, small thrombus developed in the inferior vena cava immediately after modeling in the model and inhibitor groups. The plasma levels of IL-1 and TNF-α, mRNA expression of key proteins (IL1β, Caspase-1, NLRP3, and NF-κB P65), and expression of key proteins (IL1β, Caspase-1, NLRP3, and NF-κB P65) in VTE model rats were significantly higher than inhibitor, sham operation, and normal control groups (P < 0.05). Six hours after VTE modeling, M1 type macrophages were more significantly increased than M2 type macrophages in thrombus tissue (P < 0.05).Our analyses demonstrated that the nod-like receptor protein3/Interleukin-1/nuclear factor-κB signaling pathway and macrophage polarization are important in the occurrence and development of VTE and that their target regulation may become a new strategy for VTE prevention and treatment.