The Effect Of Ethyl Pyruvate On Acute Lung Injury Induced By Sepsis

Objective To explore the effect of ethyl pyruvate on acute lung injury induced by sepsis and its possible mechanism.Methods Forty healthy adult male Sprague-Dawley rats were randomly divided into four groups using a random number table: normal control group(Normal group),sham operation group(Sham group),sepsis acute lung injury group(ALI group),and ethyl pyruvate intervention group(EP group),10 rats in each group.A rat model of sepsis was prepared by cecal ligation and puncture.In Sham group,the cecum was only flipped but not ligationed and punctured.In EP group,ethyl pyruvate solution(40mg/kg,every 6h)was injected intraperitoneally with immediately after operation.In Normal,Sham and ALI groups were injected intraperitoneally with the same amount of lactated Ringer’s solution(every 6h).The rats were killed 24 hours after model establishment.The expression levels of high mobility group box 1protein,toll-like receptor 4 and nuclear factor-κB in lung tissue homogenate were detected by enzyme-linked immunosorbent assay.The content of high mobility group box 1 protein,tumor necrosis factor-α and interleukin-10 in serum were also detected by enzyme-linked immunosorbent assay.The wet and dry lung weight ratio of lung tissue was calculated,and after hematoxylin-eosin staining,pulmonary pathological changes were observed by light microscope.Results(1)Under light microscope,the structure of lung tissue was intact in Normal and Sham groups,there was no exudation and bleeding in alveolar cavity,no edema in alveolar septum,and only a small amount of inflammatory cells infiltrated in pulmonary interstitial;In ALI group,the alveolar structure was severely damaged,there was exudation and bleeding in alveolar cavity,the alveolar septum was significantly widened,and a large number of inflammatory cells infiltration could be observed in pulmonary interstitial;Compared with ALI group,the alveolar structure of EP group was relatively intact,and the alveolar cavity exudation,hemorrhage and pulmonary interstitial inflammatory cell infiltration were significantly alleviated.(2)There were no significant difference in each detection index between Normal andSham groups(P>0.05).Compared with Sham group,the expression levels of high mobility group box 1 protein,toll-like receptor 4 and nuclear factor-κB in ALI and EP groups were increased(P<0.05);Compared with ALI group,the expression levels of high mobility group box 1 protein,toll-like receptor 4 and nuclear factor-κB in EP group were decreased(P<0.05).(3)Compared with Sham group,the concent of high mobility group box 1 protein,tumor necrosis factor-α and interleukin-10 in ALI and EP groups were increased(P<0.05);Compared with ALI group,the content of high mobility group box 1 protein and tumor necrosis factor-α in EP group were decreased,and interleukin-10 was increased(P<0.05).(4)Compared with Sham group,the wet/dry weight ratio of lung tissue in ALI and EP groups was increased(P<0.05);Compared with ALI group,the wet/dry weight ratio of lung tissue in EP group was decreased(P<0.05).Conclusion Ethyl pyruvate may reduce the inflammatory response and improve the degree of lung injury,and have a significant protective effect on acute lung injury induced by sepsis.Its mechanism may be related to the inhibition of HMGB1/TLR4/NF-κB signaling pathway.