动物造模,急性肺损伤 z-bio 2022-02-10 506

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

　　Methods Seventy-five 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. Except for the sham-operated group, the other groups were treated with cecal ligation and puncture to replicate the septic shock rat model, and the sham-operated group only underwent laparotomy. Thirty minutes before surgery, the model-LPS group was intraperitoneally injected with LPS 15 mg/kg, the model-Eto group was intraperitoneally injected with etomidate 60 mg/kg, and the model-Eto-LPS group was also intraperitoneally injected with etomidate 60 mg/kg+LPS 15 mg/kg, the model group and the sham-operated group were intraperitoneally injected with normal saline. The levels of serum endotoxin (ET), IL-1β, IL-6 and TNF-α in BALF were detected 5 h after operation, the pathological changes of lung tissue were observed, and TLR4, myeloid differentiation factor (MyD88), nuclear factor in lung tissue were detected. -κB p65 (NF-κB p65) mRNA and protein expression.

　　Results Compared with the sham operation group, the model group, model-LPS group, model-Eto group, model-Eto-LPS group had higher levels of ET and IL-1β, IL-6 and TNF-α in BALF, among which model- Eto group<model-Eto-LPS group<model group<model-LPS group (P<0.05). HE staining showed that the alveoli in the model group and model-LPS group were significantly congested, the alveolar wall and pulmonary interstitium were thickened, and a large number of inflammatory cells infiltrated, and the lesions in the model-LPS group were more serious; model-Eto group and model-Eto-LPS group The lesions were alleviated in all groups, with occasional alveolar capillary congestion and inflammatory cell infiltration, and the reduction was more obvious in the model-Eto group. Compared with the sham operation group, the relative expression levels of TLR4, MyD88, NF-κB p65 mRNA and protein in the lung tissue of the model group, model-LPS group, model-Eto group and model-Eto-LPS group were higher, and the model-Eto Group<model-Eto-LPS group<model group<model-LPS group (P<0.05).

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