Rivaroxaban down-regulates pyroptosis and the TLR4/NF-κB/NLRP3 signaling pathway to promote flap survival

Abstract

Background: Flap placement remains the primary method for wound repair, but postoperative ischemic flap necrosis is of major concern. This study explored whether rivaroxaban, a factor Xa inhibitor, enhanced flap survival.

Methods: Thirty-six rats were randomly divided into control, low-dose rivaroxaban (3 mg/kg/day), and high-dose rivaroxaban (7 mg/kg/day) groups. On postoperative day 7, the flap survival rate was analyzed and the average survival area calculated. After the rats were euthanized, immunological and molecular biological techniques were employed to assess vascular regeneration, pyroptosis, and inflammation.

Results: Rivaroxaban upregulated VEGF expression, in turn enhancing angiogenesis, and it downregulated IL-1β, IL-6, and TNF-α expression, thereby mitigating inflammation. The drug also suppressed TLR4, NF-κB p65, NLRP3, caspase-1, and IL-18 syntheses, thus inhibiting pyroptosis.

Conclusions: Rivaroxaban enhanced random flap survival by down-regulating the TLR4/NF-κB/NLRP3 signaling pathway to suppress pyroptosis, promoting vascular regeneration and inhibiting inflammation.

Keywords: Flap survival; Pyroptosis; Rivaroxaban; TLR4/NF-κB/NLRP3 signaling pathway.