STAT 活化抑制蛋白1对重症急性胰腺炎继发急性肺损伤气血屏障的影响研究.docVIP

  STAT 活化抑制蛋白 1对重症急性胰腺炎继 发急性肺损伤气血屏障的影响研究# 陈平，孙蕴伟，章永平，袁耀宗** 5 10 15 20 25 30 35 40 45 （上海交通大学医学院附属瑞金医院消化科，上海 200025） 摘要：背景及目的：既往的研究发现 STAT 活化抑制蛋白 1（PIAS1）抑制重症急性胰腺炎 （SAP）继发急性肺损伤进展，本研究旨在了解 PIAS1 在该疾病动物模型中对 Kazal 基序逆 向诱导半胱氨酸丰富蛋白（RECK）/基质金属蛋白酶（MMP）的作用，揭示其在急性肺损 伤气血屏障改变的效应和相关机制。方法：首先构建重组腺病毒 Ad5/F35-PIAS1 和 Ad5/F35-Null 质粒，3.5%牛黄胆酸钠胰胆管逆行注射诱导的大鼠 SAP 模型前 1 天分别阴茎 静脉注射 Ad5/F35-PIAS1、Ad5/F35-Null 及 PBS 液设组。 此外，造模时设假手术对照组， 16 小时后收集标本。常规观察胰腺和肺组织病理学变化及组织超微组织结构改变。行支气 管肺泡灌洗液炎性细胞计数和肺组织湿/干重系数，免疫组化测定 RECK 定位及 Western blot 检测肺组织 RECK、MMP-9、MMP-2、ICAM-1 蛋白表达。结果：Ad5/F35-PIAS1 治疗组与 Ad5/F35-Null 治疗、SAP 组分别比较，肺组织 MMP-2、MMP-9、ICAM-1 蛋白表达下调（P 0.01），而 RECK 蛋白明显升高（P0.01），随后支气管肺泡灌洗液中中性粒细胞及巨噬 细胞数降低，肺组织损伤程度包括肺损伤评分，湿/干重系数降低（P 值分别0.01），超微 结构示肺泡毛细血管间气血屏障结构破坏减轻。Ad5/F35-Null 治疗组和 SAP 组间比较， Ad5/F35-PIAS1 治疗组与对照组间比较，上述指标差异无意义（P 值分别0.05）。结论：PIAS1 高表达可能高表达 RECK 蛋白，最终抑制 MMP-2、9 蛋白表达，降低 ICAM-1 表达，维持 肺泡壁完整性，降低气血屏障通透性，抑制炎性细胞外渗，进而改善 SAP 继发急性肺损伤 炎症程度。 关键词：PIAS1；胰腺炎；急性；肺损伤；RECK；MMP The effect of PIAS1 on the blood-air barrier of severe acute pancreatitis associated with acute lung injury CHEN Ping, SUN Yunwei, ZHANG Yongping, YUAN Yaozong (Department of Gastroenterology, Shanghai Jiaotong University School of Medicine, ShangHai 200025) Abstract: BACKGROUND AND AIM: Protein inhibitor of activated STAT 1 (PIAS1) is increasingly understood to have diverse regulatory functions for inflammation，but its effect in inflammatory condition such as severe acute pancreatitis (SAP) has not previously been reported. The aim of this study was to investigate the effect of up-regulation of PIAS1 on SAP associated with acute lung injury (ALI), and its subsequent effect on the severity of disease. METHODS: SD rats were given intravenous injection of Ad5/F35-PIAS1, Ad5/F35-null or saline (SAP rats) just before induction of SAP. One group of rats underwent only sham operation as control rats. Experimental samples were harvested at 16 h after operation. Severity of pancreatic and lung injury was determined by histological methods.