胰岛素样生长因子1对全氟异丁烯吸入性肺损伤小鼠防护作用的研究

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7 d气管内滴人携带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Ⅰ型上皮细胞(AT Ⅰ)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(P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AT Ⅰ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-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AT Ⅰ是IGF-1发挥作用的可能机制.

Protective effect of insulin-like growth factor-1 on acute lung injury induced by perfluoroisobutylene inhalation in mice

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 bronchoalveolar lavage fluid (BALF), concentration of IGF-1 in serum and lung homogenate were measured. The lung pathologic changes were examined with light microscope, and ultrastructure changes in alveolar type I cells (AT I ) 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 homogenate of C group was significantly higher than that of B and D groups (all P＜0. 01). Lung hyaline membrane formation, diffuse alveolar atelectasis, 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.