Neferine Attenuates Acute Lung Injury in Sepsis Rats by Regulating NF-κB Signaling Pathway
Objective To investigate the therapeutic effect of Neferine on acute lung injury in sepsis rats and its mechanism.Methods A rat sepsis model was prepared by cecal ligation and puncture(CLP)method.After successful modeling,the rats were divided into model group,neferine low-and high-dose groups,neferine high-dose+PMA[nuclear factor kappa B(NF-κB)activator phorbol ester]group,and sham operation group was set up,with 15 rats in each group.At 6 hours after operation,the corresponding intervention was given for 2 days.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of lung tissue,and the pathological damage score was performed.The wet-dry mass ratio of lung tissue was detected;the levels of arterial partial pressure of oxygen(PaCO2)and arterial partial pressure of carbon dioxide(PaCO2)were detected by blood gas analyzer.The levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)in bronchoalveolar lavage fluid(BALF)were measured by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of NF-κB p65,phosphorylated NF-κB(p-NF-κB)p65(Ser536)and cyclooxygenase-2(COX-2)in lung tissue were detected by Western Blot.Results Compared with the sham operation group,the pathological injury of lung tissue in the model group was severe,the pathological injury score and wet-dry mass ratio of lung tissue as well as PaCO2 level were significantly increased(P＜0.01),PaO2 level was significantly decreased(P＜0.01),the levels of TNF-α,IL-1β and IL-6 in BALF,the ratio of p-NF-κB p65/NF-κB p65 and the protein expression level of COX-2 in lung tissue were significantly increased(P＜0.01).Compared with the model group,the pathological damage of lung tissue in the low-dose and high-dose neferine groups was significantly improved,the pathological damage score and wet-dry mass ratio of lung tissue as well as PaCO2 level were significantly decreased(P＜0.05 or P＜0.01),PaO2 level was significantly increased(P＜0.05 or P＜0.01),the levels of TNF-α,IL-1β and IL-6 in BALF,the ratio of p-NF-κB p65/NF-κB p65 and the protein expression level of COX-2 in lung tissue were significantly decreased(P＜0.05 or P＜0.01).However,after PMA intervention,the improvement of neferine on lung tissue injury in septic rats was significantly reversed(P＜0.01).Conclusion Neferine can improve acute lung injury and lung function in rats with sepsis,which may be related to inhibiting the activation of NF-κB signaling pathway and thereby reducing the release of inflammatory factors in vivo.
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