摘要
目的观察胰岛素样生长因子1（IGF-1）对小鼠全氟异丁烯（PFIB）吸入性急性肺损伤（ALI）模型的防护作用并探讨其可能机制。方法64只雄性昆明小鼠随机分为正常对照组（A组）、吸入PFIB染毒组（B组）、染毒前7d气管内滴入携带IGF-1基因的重组腺病毒5载体（Ad5-IGF-1）干预组（C组）、空载腺病毒对照组（D组）。使用小鼠动态吸入PFIB全身暴露染毒实验装置对小鼠进行染毒，观察各组小鼠的肺系数、支气管肺泡灌洗液（BALF）中蛋白含量、血清及肺组织中IGF-1含量，光镜下观察肺组织病理学变化及透射电镜下观察肺泡Ⅱ型上皮细胞（ATI）的变化。结果与A组比较，其他各组小鼠的肺湿／干重（W／D）比值、含水量及BALF中总蛋白含量显著增高（P均〈0．01）；C组小鼠肺W／D比值、含水量及BALF中白蛋白和总蛋白含量均较B组和D组显著下降（P均〈0．01）；B组、D组血清IGF-1含量显著低于A组，而C组IGF-1含量明显高于A、B、D组（P均〈0．01），B、C、D组肺组织匀浆中IGF-1含量较A组明显升高（尸均〈0．01），且C组显著高于B组和D组（P均〈0．01）。光镜下观察C组小鼠肺组织内透明膜形成，弥漫性肺泡不张、水肿液积聚、红细胞渗出、大量中性粒细胞及巨噬细胞聚集等病变较B组和D组明显改善；C组ATⅡ超微结构可见微绒毛脱落、细胞核皱缩、染色质致密、线粒体肿胀、双层膜结构破坏、基质空泡等改变也较B组和D组改善。结论Ad5一IGF-1对小鼠PFIB吸入性ALI具有预防作用，可以显著降低肺W／D比值、含水量及BALF中蛋白含量，提高血清及肺组织中IGF-1的含量，保护ATI是IGF-1发挥作用的可能机制。
Objective To observe the protective effect of insulin-like growth factor-1 （IGF-1） on acute lung injury induced by perfluoroisobutylene （PFIB） inhalation in mice. Methods Sixty-four male Kunming mice were randomly divided into normal control （A） group, exposed （B） group, recombinant adenoviruses 5 of IGF-1 （Ad5-IGF-1） intervention （C） group （in which Ad5-IGF-1 was injected into the trachea of the mice）, blank vector control （D） group. B, C and D groups were exposed to gaseous PFIB in a flow-past whole-body exposure system. The lung index, concentration of total protein and albuminin in bronehoalveolar lavage fluid （BALF）, concentration of IGF-1 in serum and lung homogenate were measured. The lung pathologic changes were examined with light microscope, and uhrastructure changes in alveolar type Ⅱ cells （ATⅡ ） with electron microscope. Results Compared with A group, the lung index, concentration of total protein in BALF were significantly increased in other groups, the lung index and concentration of total protein and albuminin of BALF in B and D groups were prominetly higher than C group （all P〈0. 01）. The concentration of IGF-1 in serum of B and D groups was lower markedly than that of A group, and the concentration of IGF-1 in serum of C group was distinctly higher than those of A, B, D groups （all P〈0.01）. The concentration of IGF-1 in lung homogenate of B, C, D groups was higher than that of A group, and the concentration of IGF-1 in lung bomogenate of C group was significantly higher than that of B and D groups （all P〈0.01）. Lung hyaline membrane formation, diffuse alveolar ateleetasis, accumulation of edema fluid, red blood cell exudation, were obviously milder in C group, and changes in the ultrastructure of AT I showed a similar result. Conclusion The protective effect of Ad5-IGF-1 against the toxicity of PFIB inhalation is identified. In the mice pretreated with Ad5-IGF-1 is able to significantly lower lung index, the protein concentration in BALF, and the concentration of IGF-1 in serum and lung homogenate is obviously increased. Protection of AT I may be one of the mechanisms.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2009年第4期219-221,I0002,共4页
Chinese Critical Care Medicine
基金
国家自然科学基金项目（30840039）
军队医药卫生“十一五”科研项目（06MA257）
关键词
全氟异丁烯
重组腺病毒5
胰岛素样生长因子1
急性肺损伤
perfluoroisobutylene
recombinant adenoviruses 5
insulin-like growth factor-1
acute lung injury
