الملخص
Background:Acute lung injury(ALI)is the most common organ dysfunction in severe acute pancreatitis(SAP).Somatostatin analogue octreotide is a common used drug in acute pancreatitis.Aims:To explore the protective mechanism of octreotide on lung injury in SAP mice.Methods:In the first part,the experimental mice were randomly assigned into four groups.SAP model was induced by caerulin and lipopolysaccharide,and the mice were sacrificed 24 hours,48 hours and 72 hours after establishment.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue myeloperoxidase(MPO)activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,Gasdermin D(GSDMD),interleukin(IL)-1β,IL-18 and inflammatory factors IL-6,tumor necrosis factor(TNF)-α,high mobility group protein B1(HMGB1)in lung tissue.Western blotting was used to detect protein expressions of NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,GSDMD and IL-1β in lung tissue.In the second part,mice were randomly divided into control group,SAP group,and octreotide group.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue MPO activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1.Immunofluorescence was used to detect protein expressions of NLRP3,caspase-1,GSDMD,ASC,IL-1β in lung tissue.Results:In the first part,compared with control group,pathological score of pancreas and lung tissue,serum amylase and MPO activity were significantly increased in SAP group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,GSDMD,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly increased(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD and IL-1β in lung tissue were significantly increased(all P<0.05),especially in 24 hours after establishment group.In the second part,compared with SAP group,pathological score of pancreas and lung tissue,serum amylase were significantly decreased in octreotide group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly decreased in lung tissue in octreotide group(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD,ASC and IL-1β in lung tissue were significantly decreased(all P<0.05).Conclusions:Cell pyroptosis is involved in the occurrence and development of lung injury in SAP mice,and octreotide may attenuate lung injury in SAP mice by inhibiting pyroptosis.