Emodin Modulates NLRP3/IL-1β/CXCL1 Signaling Pathway to Improve Inflammatory Response and Lung Injury in Rats with Acute Respiratory Failure
Objective:To investigate the effects of emodin on inflammatory response and lung injury in rats with acute respiratory failure,as well as its regulatory effect on the NOD like receptor protein 3(NLRP3)/interleu-kin-1β(IL-1 β)/CXC chemokine ligand 1(CXCL1)signaling pathway.Methods:A rat model of acute respiratory failure was constructed by endobronchial infusion of escherichia coli lipopolysaccharide.The 70 successful models were randomly divided into the model group,emodin low(10 mg/kg),medium(20 mg/kg),high(40 mg/kg)dose groups,emodin high dose+NLRP3 agonist[40 mg/kg emodin+10 mg/kg NLRP3 agonist(BMS-986299)]group;14 models in each group.Another 14 healthy rats were set as the control group by bronchial drip with the same amount of normal saline.The rats in each group were continuously treated with the corresponding method for 7 days(once/day).The respiratory rate,arterial partial pressure of carbon dioxide(PaCO2)and arterial partial pres-sure of oxygen(PaO2)of rats were measured by pulmonary function instrument and automatic blood gas analyzer.The inflammatory factors[tumor necrosis factor(TNF-α)and IL-8]in lung tissue were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe lung histopathology.The expression of NLRP3,IL-1β,CXCL1 messenger RNA(mRNA)and protein in lung tissue was detected by quantitative PCR and Western blotting.Results:Compared with the control group,the lung tissue structure in the model group was damaged,alveolar walls were congested,there was massive infiltration of inflammatory cells,alveo-lar edema occurred,and respiratory rate,PaCO2,lung tissue TNF-α,IL-8,NLRP3,IL-1β,CXCL1 mRNA,and pro-tein expression significantly increased,while PaO2 significantly decreased(P＜0.05);compared with the model group,in the low,medium,and high dose emodin groups,lung tissue lesions gradually alleviated,alveolar struc-tures became increasingly intact,inflammatory cell infiltration gradually decreased,respiratory rate,PaCO2,lung tis-sue TNF-α,IL-8,NLRP3,IL-1 β,CXCL1 mRNA,and protein expression decreased in a dose-dependent manner,while PaO2 increased in a dose-dependent manner(P＜0.05);compared with the high dose emodin group,in the high dose emodin+NLRP3 agonist group,lung tissue damage significantly worsened,inflammatory cell infiltration increased,respiratory rate,PaCO2,lung tissue TNF-α,IL-8,NLRP3,IL-1β,CXCL1 mRNA,and protein expression significantly increased,while PaO2 significantly decreased(P＜0.05).Conclusion:Emodin may play a protective role on lung by inhibiting NLRP3/IL-1 β/CXCL 1 signaling pathway,improving blood gas index,inflammatory re-sponse and lung injury in rats with acute respiratory failure.
Acute respiratory failureInflammatory responseLung injuryEmodinNOD like receptor protein 3Interleukin-1 βCXC chemokine ligand 1Rats
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