关键词: 依托咪酯, 脂多糖, 急性肺损伤, TXNIP/NLRP3信号通路

Abstract: Objective To investigate the effect of etomidate on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Methods The mice were randomly divided into control group, model group, etomidate groups of low (5.0 mg/kg), medium (10.0 mg/kg) and high dose (20.0 mg/kg) and positive control (Xuebijing injection, 100 μL) group with 15 mice in each. After 12 hours, the Buxco pulmonary function meter was used to detect the mouse respiratory function indicators-lung compliance, respiratory frequency, airway resistance; ELISA method was used to determine the contents of inflammatory factors-tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum of mice; the wet weight/dry weight (W/D) ratio of the mouse lungs was calculated; HE staining microscopy was used to observe the pathological changes of lung tissue in mice; Western blot was used to test the expression of TXNIP and NLRP3 proteins in mouse lung tissue. In addition, TXNIP over-expression vector (PCDNA3.1-TXNIP, 5 nmol/L) was added on the basis of 20.0 mg/kg etomidate and negative control group (pcDNA3.1) was set to explore the effect of etomidate regulation through TXNIP/NLRP3 signaling pathway on LPS-induced ALI. Results Compared with the control group, the lung tissue of the model group showed inflammatory cell infiltration and alveolar wall thickening, the lung compliance and respiratory frequency were significantly reduced (P＜0.05). The lung tissue pathology score, airway resistance, serum content of TNF-α and IL-6, lung W/D ratio, lung tissue TXNIP, NLRP3 protein expression were all increased significantly(P＜0.05). Compared with the model group, the inflammatory cell infiltration and alveolar wall thickening of the lung tissue of the mice in the etomidate low, medium and high dose groups were relieved to varying degrees and the lung compliance and respiratory frequency were gradually increased (P＜0.05). The lung tissue pathology score, airway resistance, serum TNF-α and IL-6 contents, lung W/D ratio, lung tissue TXNIP, NLRP3 protein expression were gradually decreased (P＜0.05). Compared with pcDNA3.1 group, pcDNA3.1-TXNIP group reversed protective effect of etomidate on mice. Conclusions Etomidate inhibits inflammatory response and improves pathological damage of lung tissue.

Key words: etomidate, lipopolysaccharide, acute lung injury, TXNIP/NLRP3 signaling pathway