Glabridine regulates NETs to inhibit pyrodeath and alleviate lung injury in sepsis
Objective To investigate the effect of glabridin on neutrophil extracellular traps(NETs)formation and pyroptosis in rats with sepsis-induced lung injury.Methods Twenty-four male Wistar rats were divided into three groups according to the random number table method.The sepsis group was established by cecal ligation and puncture(CLP).The Glabridin group underwent CLP and glabridin gavage(30 mg/kg)(CLP+GLA).The sham operation group underwent cecal exploration,and only the abdomen was closed after cecal turning(Sham).After 12 hours,plasma、alveolar lavage fluid and lung tissue samples were taken for detection.Then,protein content of the alveolar lavage fluid was determined;The wet/dry weight(W/D)ratio of the lung tissue was determined;The pathological changes in lung tissue were observed after hematoxylin-eosin(HE)staining.The levels of NETs marker MPO-DNA complex and related inflammatory factors IL-18 and IL-1β in plasma were detected by enzyme-linked immunosorbent assay.The changes of Caspase-land Cleaved-caspase-1 protein in lung tissue were detected by Western blot.Results The total protein concentration of alveolar lavage fluid was significantly higher in the sepsis group compared with the Sham group(P＜0.01),and it decreased in the glabridin group compared with the sepsis group(P＜0.05).Significant aggravation of pulmonary edema in the sepsis group,and the glabridin group reduced pulmonary edema compared with the sepsis group.The pathological results of lung tissue under the light microscope showed:The structure of lung tissue in the Sham group was normal,and the alveoli were clear;In the sepsis group,the alveolar wall was thickened widely and inflammatory cells infiltrated obviously;Compared with the sepsis group,the lung tissue injury was significantly reduced in the light licorice group.The enzyme-linked immunosorbent assay results showed that the levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the plasma of the sepsis group were significantly higher than those in the Sham group(P＜0.001).The levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the glabridin group were significantly lower than those in the sepsis group(MPO-DNA:P＜0.01;IL-18、IL-1β:P＜0.05).Western blot Technical results showed that the expression of Caspase-1 and Cleaved-caspase-1 protein positive signal was significantly enhanced in the lung tissue of the rats in the sepsis group compared with the Sham group;the distribution of Caspase-1 positive cells in the lung tissue of the sepsis+glabridin group was similar to that of the Sham group,and the expression of Cleaved-caspase-1 positive signal was higher than that of the Sham group.Conclusions Glabridin can effectively reduce lung inflammation and play a protective role in lung injury in septic rats by inhibiting NETs production and pyroptosis.
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