Burn injury is a devastating injury that functionally affects multiple organ systems, including the lungs, and is one of the most common serious injuries worldwide and an increasingly serious public health problem. Multiple organ failure is the leading cause of 70% of burn-related deaths (Krishnan et al., 2013). Moreover, exaggerated inflammation can lead to tissue and organ destruction, systemic inflammatory response syndrome, multiple organ dysfunction syndrome and even death. Acute lung injury (ALI) is a common complication in burn patients with burn areas exceeding 30% of the total surface area (Schmid et al., 1997). Severe burns without inhalation injury are also a common cause of acute respiratory distress syndrome (ARDS) (Liffner et al., 2005; Turnage et al., 2002). A multimodal treatment approach is required because the intense inflammatory response to burns can lead to multiple organ failure, and extensive skin damage increases the risk of infection, especially in the lung, after burn injury. A specific therapeutic agent is necessary to attenuate lung injury secondary to burns.

Burns can upregulate cyclooxygenase-2 (COX2) (Li et al., 2016), and COX2 activity can lead to long-term ALI after burn injury (Sio et al., 2010). As a nonsteroidal anti-inflammatory drug, parecoxib sodium reduces the inflammatory response by selectively inhibiting COX2 expression and reducing prostaglandin formation (Bian et al., 2018; Yan et al., 2021). In the present study, the role of parecoxib sodium in lung injury was explored. Parecoxib sodium is increasingly used as an analgesic agent after noncardiac surgery (Shen et al., 2015; Yang et al., 2015). Parecoxib sodium can downregulate the expression of IL-1β, IL-6 and TNF-α in the spinal cord to achieve analgesic effects (Chen et al., 2019). Parecoxib sodium significantly inhibits the inflammatory cascade, evidenced by attenuations in TNF-α and IL-6, and significantly inhibits the expression of iNOS after ischemia‒reperfusion (I/R) (Zhang et al., 2015). Parecoxib mitigates I/R injury in the lung by suppressing inflammation and oxidative stress (Qin et al., 2021) and alleviates ventilator-induced lung injury by modulating lung function (Zhang et al., 2021) and improving gas exchange and epithelial permeability (Meng et al., 2017). Paracoxib has also been reported to reduce systemic inflammation and ALI in burned rats (Chong et al., 2014). However, the exact molecular mechanism by which paracoxib ameliorates ALI induced by burns remains to be further explored. In M1 macrophages, high levels of TNF-α and iNOS were found to mediate tissue damage and trigger inflammatory responses (Dall'Asta et al., 2012; Mantovani et al., 2013). High expression of IL-10 was one of the characteristics of M2 macrophages involved in tissue remodel and repair (Mantovani et al., 2002; Martinez and Gordon, 2014). iNOS and CD86 are markers of M1 macrophages (Porta et al., 2015; Wang et al., 2014) as well as CD206 is a marker of M2 macrophages(Mily et al., 2020; Väyrynen et al., 2021). The polarization of M1/M2 macrophages is reported involved in inflammation. Therefore, the effect of parecoxib on edema after burn injury involving the polarization of M1/M2 macrophages and related TLR4/NF-κB signalling pathway, and the expression of different inflammatory factors response to burns were investigated.

In the present study, the wound tissue and serum were collected from an in vivo deep Ⅱ back burn mouse model. The effect of parecoxib sodium on burned mice was investigated to determine whether it can regulate the polarization of M1/M2 macrophages by inhibiting the TLR4/NF-κB signalling pathway and thereby alleviate the inflammatory response. The specific molecular mechanisms by which parecoxib sodium regulates lung injury were also explored through in vitro studies to further confirm the effect of parecoxib sodium on TLR4/NF-κB signalling pathway in regulating the polarization of M1/M2 macrophages, and to clarify the reparative role of parecoxib sodium in organ protection after burn injury.