细胞凋亡在大鼠急性肺损伤发生机制中的意义  

The role of apoptosis in the pathogenesis of acute lung injury in rats

作　　者：王颖[1] 张淑文[1] 王宝恩[1] 

机构地区：[1]首都医科大学附属北京友谊医院感染内科,北京100050

出　　处：《中国危重病急救医学》2001年第2期90-94,共5页Chinese Critical Care Medicine

基　　金：北京市卫生局科研基金资助项目(No.A165)

摘　　要：目的 :从细胞凋亡的角度探讨急性肺损伤 (AL I)的发病机制。方法 :Wistar大鼠 48只 ,随机分成 2组 :1模型组 (AL I组 ) 30只 ,静注标准大肠杆菌菌株制成 AL I模型 ,分别于给药后 4、8及 12小时采集样品 (各时间点 10只 ) ;2对照组 18只 ,静注等量生理盐水 ,同模型组时间点采样 (各时间点 6只 )。观察肺组织病理切片 ,监测动脉血氧分压 (Pa O2 )、肺系数 (L I)、肺通透指数 (L PI)及肿瘤坏死因子α(TNFα) ;以电镜、流式细胞术和原位末端标记法 (TU NEL )检测凋亡细胞。结果 :AL I组给药后 4小时起光镜下可见肺组织肺泡腔狭窄、中性粒细胞渗出等 AL I表现 ,且随时程延长病变加重。Pa O2 降低 ,L I、L PI及 TNFα增高 ,与对照组相比有显著性差异 (P均 <0 .0 1)。 TUNEL 染色结果 :AL I组部分肺组织细胞呈阳性染色 ,流式细胞术显示 AL I组 4、8及12小时凋亡细胞分别为 (7.15± 1.2 6 ) %、(12 .39± 1.6 7) %和 (6 .72± 1.11) % ,与对照组相比较 ,P均 <0 .0 1。结论 :细胞凋亡在急性肺损伤发生机制中起重要作用 ,通过 TNFα的作用 ,促进 AL I时的炎症反应。细胞凋亡随肺损伤时程延长呈先增加后下降趋势 ,且总体处于低水平。Objective:To investigate the potential role of apoptosis in the development of acute lung injury (ALI).Methods:Fortyeight Wistar rats were randomly divided into two groups.In ALI group,30 animals were intravenously infused with standard E.coli to reproduce the ALI model,and the samples were collected at 4,8 and 12 hours after bacterial challenge respectively.In sham operation group,18 animals were intravenously infused with normal saline in equal volume and the samples were obtained at same intervals.The parameters of ALI including blood gas,lung index(LI),lung permeability index (LPI),tumor necrosis factorα (TNFα) and pulmonary pathology were determined.Apoptosis was detected by transmission electronmicroscopy,flow cytometry and TdTmediated dUTP nick end labeling (TUNEL),respectively.Results:It was observed that alveolar spaces were narrowed and neutrophils exuded at 4 hours after E.coli challenge.With prolongation of time the pulmonary damage was worsened.PaO 2 decreased,LI,LPI and TNFα increased,and the differences were significant between ALI group and sham operation group (all P <0 01).TUNEL results showed that in ALI group,a part of cells were positive,and apoptotic cells were (7 15±1 26)%,(12 39±1 67)%,(6 72±1 11)% at 4,8 and 12 hours,respectively,as detected by flow cytometry (all P <0 01).Conclusions:Apoptosis may play an important role in the pathogenesis of ALI.Apoptosis,as a pathogenetic mechanism,accelerates the inflammatory responses of ALI modulated by TNFα.With prolongation of ALI,apoptosis initially increased and then declined,keeping a low level.

关 键 词：细胞凋亡 肺损伤 急性 

分 类 号：R654.3[医药卫生—外科学]