[Animal modeling] - Study on the protective effect of etomidate based on TLR4 pathway on acute lung injury in rats with septic shock

  Objective To investigate the protective effect of etomidate (Eto) based on Toll like receptor 4 (TLR4) pathway on acute lung injury in septic shock rats.

  Methods 75 rats were randomly divided into sham operation group, model group, model lipopolysaccharide (LPS) group, model Eto group and model Eto LPS group, with 15 rats in each group. In addition to the sham operation group, the other groups used cecal ligation and puncture method to duplicate the rat model of septic shock, and the sham operation group only performed laparotomy. Thirty minutes before operation, LPS 15 mg/kg was intraperitoneally injected into model LPS group, etomidate 60 mg/kg was intraperitoneally injected into model ETO group, etomidate 60 mg/kg+LPS 15 mg/kg was intraperitoneally injected into model ETO LPS group, and normal saline was intraperitoneally injected into model group and sham operation group. Serum endotoxin (ET) level and IL-1 in BALF were detected 5 h after operation β、 IL-6、TNF- α, Observe the pathological changes of lung tissue and detect TLR4, MyD88 and nuclear factor in lung tissue- κ B p65(NF- κ B p65) mRNA and protein expression.

  Results Compared with sham operation group, ET content in model group, model LPS group, model Eto group, model Eto LPS group and IL-1 in BALF β、 IL-6、TNF- α The levels were all high, including model Eto group<model Eto LPS group<model group<model LPS group (P<0.05). HE staining showed that the alveoli in model group and model LPS group were obviously congested, the alveolar wall and pulmonary interstitium were thickened, and a large number of inflammatory cells were infiltrated, and the disease in model LPS group became serious; The pathological changes in model Eto group and model Eto LPS group were alleviated, occasionally with alveolar capillary congestion and inflammatory cell infiltration, and the reduction in model Eto group was more obvious. Compared with sham operation group, TLR4, MyD88, NF in lung tissue of model group, model LPS group, model Eto group, model Eto LPS group- κ The relative expression of Bp65 mRNA and protein was high, including model Eto group<model Eto LPS group<model group<model LPS group (P<0.05).

  Conclusion Eto has protective effect on acute lung injury in septic shock rats, which may play a regulatory role by inhibiting TLR4 pathway.