Dexmedetomidine alleviates LPS-induced acute lung injury via regulation of the p38/HO-1 pathway

Acute lung injury (ALI) is a common critical illness in clinical anesthesia and the intensive care unit that can cause acute hypoxic respiratory insufficiency. Despite various therapeutic regimes having been investigated, there is currently no effective pharmacotherapy available to treat ALI. Previous studies have reported that the NOD-like receptor protein 3 (NLRP3) signaling pathway plays an important role in the inflammatory response and is involved in the pathogenesis of ALI. Moreover, dexmedetomidine (Dex), an α2-adrenergic receptor activating agent, has been routinely used as an adjuvant therapy in treating inflammatory diseases, including ALI. However, the precise pathological mechanisms of Dex in ALI remain to be elucidated. Thus, the present study aimed to investigate the effects of the p38/heme oxygenase 1 (HO-1) signaling pathways in the pathological mechanisms of Dex in ALI. Newborn male Sprague-Dawley rats (n=48) were randomly divided into four groups (n=12 each), and an intravenous injection of lipopolysaccharide (LPS) was used to successfully induce the ALI model, with increased pulmonary damage, cell apoptosis, interleukin-1β (IL-1β) secretion and edema fluid in lungs. Moreover, the mRNA and protein expression levels of NLRP3 were significantly upregulated, while that of HO-1 were downregulated by LPS treatment. Furthermore, the levels of phosphorylated p38 were also upregulated in ALI rats. It was demonstrated that Dex administration significantly alleviated LPS-induced ALI, downregulated the secretion of IL-1β, decreased the expression of NLRP3, inhibited the phospho-activation of p38 and increased HO-1 expression. In addition, pharmacological inhibition of p38 using the inhibitor SB20380 further enhanced the effect of Dex. Collectively, these preliminarily results identified the effects of Dex intervention on the pathogenesis of ALI via the regulation of p38/HO-1 signaling pathways, which impacted the inflammatory effects, thus providing a theoretical basis and novel evidence for the development of new targets for clinical treatment of ALI.