生长抑素类似物奥曲肽对重症急性胰腺炎小鼠肺损伤保护机制的研究  

Study on Mechanism of Somatostatin Analogue Octreotide in Protecting Against Lung Injury in Mice With Severe Acute Pancreatitis

作　　者：赵梦琦 崔梦妍 陈素敏 陆颖影[1,2] 江巧丽 ZHAO Mengqi;CUI Mengyan;CHEN Sumin;LU Yingying;JIANG Qiaoli(Department of Gastroenterology,Jiading Branch of Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,210803;Department of Gastroenterology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai)

机构地区：[1]上海市第一人民医院嘉定医院/上海市嘉定区江桥医院消化内科,201803 [2]上海交通大学医学院附属第一人民医院消化内科

出　　处：《胃肠病学》2023年第6期326-334,共9页Chinese Journal of Gastroenterology

基　　金：上海市嘉定区卫生健康委员会科研课题计划(2022-KY-01)。

摘　　要：背景:急性肺损伤(ALI)是重症急性胰腺炎(SAP)最常见的器官功能障碍。生长抑素类似物奥曲肽是临床上用于治疗急性胰腺炎的常见药物。目的:探讨奥曲肽对SAP小鼠肺损伤的保护机制。方法:第一部分实验小鼠随机分为4组,采用雨蛙肽联合脂多糖诱导SAP模型,造模后24 h、48 h、72 h处死小鼠。HE染色观察胰腺和肺组织病理学评分,检测血清淀粉酶、肺组织髓过氧化物酶(MPO)活性,应用实时荧光定量PCR法检测肺组织中焦亡相关分子caspase-1、凋亡相关斑点样蛋白(ASC)、Gasdermin D(GSDMD)、白细胞介素(IL)-1β、IL-18和炎症因子IL-6、肿瘤坏死因子-α(TNF-α)、高迁移率族蛋白B1(HMGB1) mRNA表达,蛋白质印迹法检测肺组织中NOD样受体热蛋白结构域相关蛋白3(NLRP3)、caspase-1、GSDMD和IL-1β蛋白表达。第二部分实验小鼠随机分为对照组、SAP组和奥曲肽组,HE染色观察胰腺和肺组织病理学评分,检测血清淀粉酶和肺组织MPO活性,实时荧光定量PCR法检测肺组织中焦亡相关分子caspase-1、ASC、IL-1β、IL-18和炎症因子IL-6、TNF-α、HMGB1 mRNA表达,免疫荧光染色法检测肺组织中NLRP3、caspase-1、GSDMD、ASC和IL-1β蛋白表达。结果:第一部分实验中,与对照组相比,SAP组小鼠胰腺和肺组织病理学评分、血清淀粉酶以及MPO活性均显著升高(P均<0.05),肺组织焦亡相关分子caspase-1、ASC、GSDMD、IL-1β、IL-18和炎症因子IL-6、TNF-α、HMGB1 mRNA表达显著升高(P均<0.05),NLRP3、caspase-1、GSDMD和IL-1β蛋白表达显著升高(P均<0.05),其中造模24 h组升高最为明显。第二部分实验中,与SAP组相比,奥曲肽组胰腺和肺组织病理学评分显著降低(P均<0.05);血清淀粉酶显著降低(P<0.05);肺组织焦亡相关分子caspase-1、ASC、IL-1β、IL-18以及炎症因子IL-6、TNF-α、HMGB1 mRNA表达显著降低(P均<0.05);肺组织中NLRP3、caspase-1、GSDMD、ASC和IL-1β蛋白表达显著降低(P均<0.05)。结论:细�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⁃1βin 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⁃1βin 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 e

关 键 词：奥曲肽 重症急性胰腺炎 肺损伤 细胞焦亡 治疗 

分 类 号：R576[医药卫生—消化系统]