PIAS1对重症急性胰腺炎继发急性肺损伤血气屏障影响的研究  

Effect of PIAS1 on Blood-air Barrier of Acute Lung Injury in Severe Acute Pancreatitis

作　　者：陈平[1] 孙蕴伟[1] 章永平[1] 袁耀宗[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院消化内科,200025

出　　处：《胃肠病学》2013年第6期330-335,共6页Chinese Journal of Gastroenterology

基　　金：国家自然科学基金(81170437);博士学科点专项科研基金新教师类资助课题(2011073120001)资助

摘　　要：背景:研究发现STAT活化抑制蛋白1(PIAS1)可抑制急性坏死性胰腺炎(ANP)继发急性肺损伤,但机制尚不明确。目的:探讨PIAS1对ANP大鼠继发急性肺损伤血气屏障的作用及其机制。方法:构建重组腺病毒Ad5/F35-PIAS1和Ad5/F35-Null质粒。以3.5%牛磺胆酸钠胰胆管逆行注射诱导大鼠ANP模型,并于造模前1 d分别经阴茎静脉注射Ad5/F35-PIAS1、Ad5/F35-Null和PBS液,设立假手术组作为对照。造模16 h后处死大鼠。观察胰腺和肺组织的病理学变化和超微结构改变。测定支气管肺泡灌洗液炎性细胞计数和肺组织湿/干重系数,以免疫组化法检测RECK定位表达,蛋白质印迹法检测肺组织RECK、MMP-2、MMP-9、ICAM-1蛋白表达。结果:与ANP组和Ad5/F35-Null组相比,Ad5/F35-PIAS1组胰腺和肺组织病理学明显改善,肺组织病理学评分显著降低(P<0.01),超微结构示肺泡毛细血管间血气屏障结构破坏减轻;支气管肺泡灌洗液中性粒细胞和巨噬细胞计数、湿/干重系数均显著降低(P<0.01);肺组织RECK蛋白表达显著升高(P<0.01),MMP-2、MMP-9、ICAM-1蛋白表达显著下调(P<0.01);Ad5/F35-PIAS1组上述指标与对照组相比均无明显差异(P>0.05)。结论:PIAS1可能通过增强RECK蛋白表达、抑制MMP-2、MMP-9、ICAM-1蛋白表达,降低血气屏障通透性,抑制炎性细胞外渗,进而改善ANP继发急性肺损伤的炎症程度。Background： Protein inhibitor of activated STAT 1（PIAS1） is increasingly known to be capable of inhibiting the acute lung injury（ALI） associated with acute necrotizing pancreatitis（ANP）,but its mechanism has not been elucidated.Aims： To investigate the effect and mechanism of PIAS1 on blood-air barrier of ALI associated with ANP.Methods： Recombinant adenovirus Ad5 / F35-PIAS1 and Ad5 / F35-Null plasmids were constructed.ANP was induced in rats by retrograde injection of 3.5% sodium taurocholate into the pancreaticobiliary duct.One day before induction of ANP,rats were given intravenous injection of Ad5 / F35-PIAS1,Ad5 / F35-Null or PBS,respectively.Rats underwent sham operation were served as controls.Rats were sacrificed 16 hours after the establishment of ANP model.Changes of pathology and ultrastructure of pancreatic and lung tissue were observed.Count of inflammatory cells in broncho-alveolar lavage fluid and wet / dry weight index of lung tissue were detected.Location of RECK was detected by immunohistochemistry.Protein expressions of RECK,MMP-2,MMP-9 and ICAM-1 in lung tissue were determined by Western blotting.Results： Compared with ANP group and Ad5 / F35-Null group,pancreatic and lung injury in Ad5 / F35-PIAS1 group was significantly ameliorated,pathological score of lung tissue was significantly decreased（P〈0.01）,ultrastructure showed that destroy of blood-air barrier of alveolar blood capillary was ameliorated;counts of neutrophil and macrophage in broncho-alveolar lavage fluid and wet / dry weight index were significantly decreased（P〈0.01）;expression of RECK protein in lung tissue was significantly increased（P〈0.01）,while expressions of MMP-2,MMP-9 and ICAM-1 proteins in lung tissue were significantly decreased（P〈0.01）.However,no significant differences in above-mentioned indices were found between Ad5 / F35-PIAS1 group and controls（P〈0.05）.Conclusions： The findings suggest that PIAS1 could decrease the pulmonary blood-air permeability and inhibit in

关 键 词：STAT活化抑制蛋白1 胰腺炎 急性坏死性 急性肺损伤 RECK 基质金属蛋白酶类 

分 类 号：R576[医药卫生—消化系统]