Effect of Sufentanil on Lung Injury in Rats with Severe Pneumonia by Regulating TLR4/MyD88/NF-κB Pathway
Objective:To investigate the effects of sufentanil(Sufen)on lung injury in rats with severe pneumonia(SP)and the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)pathway.Methods:An SP rat model was constructed;the successfully modeled rats were grouped into severe pneumonia group(SP group),low-dose and high-dose sufentanil groups(Sufen-L,Sufen-H groups),and high-dose sufentanil+TLR4 activator LPS group(Sufen-H+LPS group),with 24 rats in each group.An additional 24 normal rats were used as the Control group.The levels of inflammatory factors in alveolar lavage fluid and the number of inflammatory cells in alveolar lavage fluid sediment were detected.The wet to dry weight ratio(W/D)of lung tissue was measured.HE staining was applied to observe the path-ological changes in lung tissue of rats in each group.Western blot was applied to detect the expression levels of TLR4,MyD88,p-NF-κB p65/NF-κB p65 in lung tissue.Results:The lung tissue in the SP group was more severely damaged than that in the Control group,with thickening of the lung interstitium,alveolar ede-ma,and extensive infiltration of inflammatory cells,the levels of TNF-α,IL-1β,IL-6,numbers of EOS and NEU inflammatory cells,W/D ratio,the protein expression of TLR4,MyD88,and p-NF-κB p65/NF-κB p65 were greatly increased(P＜0.05).Compared with the SP group,the Sufen-L and Sufen-H groups showed reduced lung tissue damage,gradually intact alveolar structure,reduced edema,and reduced infiltra-tion of inflammatory cells,the levels of TNF-α,IL-1β,IL-6,numbers of EOS and NEU inflammatory cells,W/D ratio,the protein expression of TLR4,MyD88,and p-NF-κB p65/NF-κB p65 were greatly reduced,and the Sufen-H group was superior to the Sufen-L group(P＜0.05).Compared with the Sufen-H group,the Sufen-H+LPS group had more severe lung tissue damage,severe alveolar structural damage,great alveo-lar edema,and increased inflammatory cell infiltration in rats,the levels of TNF-α,IL-1β,IL-6,numbers of EOS and NEU inflammatory cells,W/D ratio,the protein expression of TLR4,MyD88,and p-NF-κB p65/NF-κB p65 were greatly increased(P＜0.05).Conclusion:Sufen improves lung injury in rats with SP and is associated with inhibition of the TLR4/MyD88/NF-κB signaling pathway.
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