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中华损伤与修复杂志(电子版) ›› 2018, Vol. 13 ›› Issue (05) : 342 -347. doi: 10.3877/cma.j.issn.1673-9450.2018.05.005

所属专题： 文献；

论著

酸性成纤维细胞生长因子对大鼠急性肺损伤的影响
李世元1, 岳红云2, 张湘华2, 罗园2,†()   
  1. 1. 050011　石家庄，河北医科大学附属人民医院烧伤科
    2. 050011　石家庄，河北医科大学附属人民医院呼吸一科
  • 收稿日期:2018-07-01 出版日期:2018-10-01
  • 通信作者: 罗园
  • 基金资助:
    河北省医学科学研究重点课题(20181000)

Effect of acid fibroblast growth factor on lipopolysaccharides-induced acute lung injury in rat

Shiyuan Li1, Hongyun Yue2, Xianghua Zhang2, Yuan Luo2,†()   

  1. 1. Department of Burns, Affiliated People′s Hospital of Hebei Medical University, Shijiazhuang 050011, China
    2. Department of Respiratory, Affiliated People′s Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Received:2018-07-01 Published:2018-10-01
  • Corresponding author: Yuan Luo
  • About author:
    Corresponding author: Luo Yuan, Email:
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引用本文：

李世元, 岳红云, 张湘华, 罗园. 酸性成纤维细胞生长因子对大鼠急性肺损伤的影响[J]. 中华损伤与修复杂志(电子版), 2018, 13(05): 342-347.

Shiyuan Li, Hongyun Yue, Xianghua Zhang, Yuan Luo. Effect of acid fibroblast growth factor on lipopolysaccharides-induced acute lung injury in rat[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2018, 13(05): 342-347.

目的

探讨酸性成纤维细胞生长因子(aFGF)对脂多糖诱导的大鼠急性肺损伤(ALI)的作用及其影响机制。

方法

将60只雄性SD大鼠按照随机数字表法分为3组：阴性对照组、脂多糖损伤组、aFGF干预组，每组20只。采用经气管插管给予脂多糖5 mg·kg－1制备大鼠ALI模型，aFGF干预组则于给予脂多糖24 h后，经气道给予aFGF 1 000 μ·g－1。3组均于48 h后苏木精-伊红染色观察肺组织病理学改变，计算肺损伤评分，测定肺水清除率，称量肺湿/干重比，免疫组织化学染色法观察肺泡表面活性蛋白C(SP-C)的表达，酶联免疫吸附试验法测定肺泡灌洗液中肿瘤坏死因子α(TNF-α)的水平。蛋白质印迹法检测肺组织磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)蛋白表达水平。数据采用单因素方差分析(进一步两两比较采用LSD法)或非参数检验。

结果

(1)aFGF干预组肺损伤评分[(6.33±0.42)分]与脂多糖损伤组肺损伤评分[(11.00±0.37)分]较阴性对照组[(1.01±0.26)分]均升高，但aFGF干预组肺损伤评分明显低于脂多糖损伤组，差异有统计学意义(P<0.05)。(2)aFGF干预组肺水清除率[(27.41±1.05)%]与脂多糖损伤组肺水清除率[(15.59±0.64)%]较阴性对照组[(30.63±0.91)%]均有所下降，但aFGF干预组明显高于脂多糖损伤组，差异均有统计学意义(P<0.05)。(3)脂多糖损伤组肺水聚集(肺湿/干重比为6.32±0.32)较阴性对照组(4.17±0.05)明显升高，aFGF干预组(5.18±0.10)也高于阴性对照组，但与脂多糖损伤组相比，肺湿/干重比有所改善且差异有统计学意义(P<0.05)。(4)aFGF干预组TNF-α水平[(762.50±23.93) pg/mL]与脂多糖损伤组TNF-α水平[(1460.01±17.96) pg/mL]较阴性对照组[(49.51±10.75) pg/mL]均明显升高，但aFGF干预组较脂多糖损伤组有明显下降，差异均有统计学意义(P<0.05)。(5)aFGF干预组p-p38 MAPK/β-actin比值(0.38±0.01)明显高于阴性对照组(0.18±0.01)，差异有统计学意义(P<0.05)，且明显高于脂多糖损伤组(0.12±0.01)，差异有统计学意义(P<0.01)。

结论

aFGF对脂多糖诱导的ALI大鼠具有肺保护作用，其机制可能为aFGF通过激活p38 MAPK通路，减少细胞凋亡，促进肺泡上皮细胞再生所致。

关键词: 成纤维细胞生长因子1, 急性肺损伤, 脂多糖类, 肺水清除率
Objectives

To investigate the effect of acid fibroblast growth factor(aFGF) on lipopolysaccharides-induced acute lung injury in rat.

Methods

Sixty male SD rats were divided into three groups according to the random number table: negative control group, lipopolysaccharide injury group and aFGF intervention group, with 20 rats in each group. Acute lung injury model of rats was prepared using lipopolysaccharide 5 mg·kg-1 via endotracheal intubation, and aFGF intervention group received aFGF 1 000 μ·g-1 via airway after 24 hours of lipopolysaccharide administration. Three groups are in 48 h after hematoxylin eosin staining to observe the lung tissue pathology change, lung injury score calculation, the determination of lung water clearance, weighing lung wet/dry weight ratio(W/D), immunohistochemical staining to observe the alveolar surface activated protein C (SP-C) expression of enzyme-linked immunosorbent assay method determination of tumor necrosis factor alpha (TNF-α) in alveolar lavage levels. The protein expression level of p38 mitogen-activated protein kinase (p-p38MAPK) in lung tissue was detected by protein imprinting. The data were analyzed by single factor anova (LSD method for further pairwise comparison) or non-parametric test.

Results

(1) Among the lung injury scores, both the aFGF intervention group [(6.33±0.42) points] and the lipopolysaccharide injury group [(11.00±0.37) points] were increased compared with the negative control group [(1.01±0.26) points], but the lung injury score of the aFGF intervention group was significantly lower than the lipopolysaccharide injury group, the differences were statistically significant (P<0.05). (2) In terms of lung water clearance rate, the level of AFC in aFGF group [(27.41±1.05)%] and the lipopolysaccharide injury group [(15.59±0.64)%] were decreased compared with the negative control group [(30.63±0.91)%], but the aFGF group was significantly higher than the lipopolysaccharide injury group, the differences were statistically significant (P<0.05). (3) W/D in the lipopolysaccharide injury group (6.32 ±0.32) was significantly higher than the negative control group (4.17±0.05), and the aFGF group (5.18 ±0.10) was also higher than the control group, but W/D was improved and the difference was statistically significant compared with the lipopolysaccharide injury group (P<0.05). (4) The level of TNF-α in aFGF group [(762.50±23.93) pg/mL] and lipopolysaccharide injury group [(1460.01±17.96) pg/mL] were significantly increased compared with the control group [(49.51 ±10.75) pg/mL], but the aFGF group was significantly decreased compared with the lipopolysaccharide injury group, the differences were statistically significant (P<0.05). (5) In terms of p-p38 MAPK expression, the p-p38 MAPK/ cycle-actin ratio of aFGF intervention group(0.38±0.01) was significantly higher than that of the negative control group (0.18±0.01), the differences were statistically significant (P<0.05) and significantly higher than that of the lipopolysaccharide injury group (0.12±0.01) (P<0.01).

Conclusions

Acid fibroblast growth factor plays an important role in acute lung injury treatment. It can decrease the apoptosis of injured lung cells, increase the AFC, improve the ability of lungs to clear fluid, which is of clinical significance.

Key words: Fibroblast growth factor 1, Acute lung injury, Lipopolysaccharides, Alveolar fluid clearance
表1 各组大鼠肺损伤评分、肺水清除率、肺部湿重/干重、肺泡灌洗液中肿瘤坏死因子α水平表达的变化(±s)
组别 例数 肺损伤评分(分) 肺水清除率(%) 湿重/干重 肿瘤坏死因子α(pg/mL)
阴性对照组 20 1.01±0.26 30.63±0.91 4.17±0.05 49.51±10.75
脂多糖损伤组 20 11.00±0.37 15.59±0.64 6.32±0.32 1 460.01±17.96
aFGF干预组 20 6.33±0.42 27.41±10.50 5.18±0.10 762.50±23.93
F值 ? 3972.26 62.25 632.70 2955.43
P值 ? <0.001 <0.001 <0.001 <0.001
图1 阴性对照组、脂多糖损伤组及aFGF干预组大鼠肺组织病理结构变化(苏木精－伊红染色×200)。A示阴性对照组保持基本肺泡完整结构；B示脂多糖损伤组肺泡完整结构破坏，肺泡间隔增厚，中性粒细胞聚集及肺泡腔纤维蛋白渗出；C示aFGF干预组肺泡间隔增厚明显减轻，炎症浸润减少，结构破坏减少
图2 SP-C在阴性对照组、脂多糖损伤组及aFGF干预组大鼠肺组织中表达(SP-C染色×200)。A示阴性对照组SP-C常规表达；B示脂多糖损伤组SP-C在大鼠肺组织中表达明显减低；C示aFGF干预组SP-C在肺组织中表达有所上调，但仍不能达到阴性对照组水平
图3 蛋白质印迹法检测各组大鼠肺组织中p－p38MAPK蛋白表达
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