L-精氨酸诱导小鼠急性坏死性胰腺炎肠屏障损伤的实验研究  

Study on Intestinal Barrier Injury in Acute Necrotizing Pancreatitis Induced by L-Arginine in Mice

作　　者：黄则华 梅启享 黄春兰[1] 陆颖影 曾悦[1] HUANG Zehua;MEI Qixiang;HUANG Chunlan;LU Yingying;ZENG Yue(Department of Gastroenterology,Shanghai General Hospital,Shanghai Jiao Tong University,Shanghai,201620)

机构地区：[1]上海交通大学附属第一人民医院消化科,201620

出　　处：《胃肠病学》2020年第5期283-287,共5页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金(81970555,81600500);上海申康医院发展中心临床研究培育项目(SHDC12017X09);上海交通大学医学院高峰高原计划—“研究型医师”项目(20181813)。

摘　　要：背景:研究表明,肠屏障功能障碍与急性坏死性胰腺炎(ANP)的发生、发展密切相关。目的:探讨L-精氨酸诱导的ANP小鼠肠屏障损伤及其加重ANP的机制。方法:将30只C57BL/6小鼠随机分为假手术组(SO组)和ANP组。ANP组小鼠给予腹腔注射8%L-精氨酸(4.5 g/kg)共两次,间隔为1 h;SO组则腹腔注射等体积0.9%NaCl溶液。造模24 h、48 h和72 h后处死小鼠,行HE染色评估胰腺和肠道病理学评分,检测血清淀粉酶、脂肪酶水平,以ELISA法评估炎症因子(IL-1β、IL-6、TNF-α)和肠道通透性(DAO、D-乳酸、LPS)水平,蛋白质印迹法检测胰腺组织和肠道组织TLR4、MyD88蛋白表达。结果:与SO组相比,ANP组相应时间点胰腺组织和回肠组织病理学评分显著增高(P<0.05),血清淀粉酶、脂肪酶、炎症因子(IL-1β、IL-6、TNF-α)、肠道通透性指标(DAO、D-乳酸、LPS)水平均显著增高(P<0.05),胰腺组织和回肠组织TLR4、MyD88蛋白表达显著增高(P<0.05)。结论:L-精氨酸诱导的ANP小鼠肠道通透性增加,LPS释放增多,可能通过激活TLR4-MyD88信号通路促进肠道、全身炎症反应,进而加重ANP。Background:Studies have indicated that dysfunction of intestinal barrier is closely related to the occurrence and development of acute necrotizing pancreatitis(ANP).Aims:To investigate the intestinal barrier injury in mice with ANP induced by L-arginine and its mechanism on aggravating ANP.Methods:Thirty C57BL/6 mice were randomly divided into sham-operation(SO)group and ANP group.Mice in ANP group were intraperitoneally injected with 8%L-arginine(4.5 g/kg)twice at an interval of 1 hour,while mice in SO group were intraperitoneally injected with an equal volume of 0.9%NaCl solution.Mice were sacrificed 24,48,72 hours after the establishment of ANP.HE staining was used to evaluate the pathological score of pancreas and intestine.Serum amylase,lipase were determined.Inflammatory factors(IL-1β,IL-6,TNF-α)and intestinal permeability(DAO,D-lactic acid,LPS)were measured by ELISA assay.Western blotting was used to detect protein expressions of TLR4,MyD88 in pancreatic tissue and ileal tissue.Results:Compared with SO group,histopathological score of pancreatic tissue and ileal tissue were significantly increased at corresponding-time in ANP group(P<0.05),serum levels of amylase,lipase,inflammatory factors(IL-1β,IL-6,TNF-α)and intestinal permeability(DAO,D-lactic acid,LPS)were significantly increased(P<0.05),protein expressions of TLR4,MyD88 in pancreatic tissue and ileal tissue were significantly increased(P<0.05).Conclusions:Intestinal permeability is increased in ANP mice induced by L-arginine,and the secretion of LPS is increased,which may enhance the intestinal inflammation and systematic inflammation via activating TLR4-MyD88 signaling pathway,thereby aggravating ANP.

关 键 词：胰腺炎 急性坏死性 精氨酸 肠道屏障 TOLL样受体4 髓样分化因子88 

分 类 号：R28[医药卫生—中药学]