角质细胞生长因子对吸入高体积分数氧新生大鼠肺转化生长因子β1表达的影响

Effect of keratinocyte growth factor on the lung tissue and expression of transforming growth factor - β1 in newborn rats with hyperoxia

目的：研究角质细胞生长因子（KGF）对高体积分数氧（高氧）暴露下新生大鼠肺组织及转化生长因子β1（TGF-β1）表达的影响。方法将108只新生 SD 大鼠按随机数字表法机分为空气组、高氧组和 KGF 干预组，每组36只。每组又分为3、7、14 d 3个亚组，每组12只。高氧组、KGF 干预组大鼠持续暴露于氧体积分数﹥950 mL/ L 氧箱中，KGF 干预组于吸氧同时背部皮下注射重组人 KGF（rhKGF）1 mg/ d，连用3 d 后改为0.5 mg/ d直至实验结束；空气组和高氧组注射等量9 g/ L 盐水。空气组大鼠呼吸空气。3、7、14 d 亚组在相应时间点取肺组织，分别采用 HE 染色和免疫组织化学方法观察各组大鼠肺组织形态变化并检测 TGF-β1蛋白表达水平。结果空气组7 d 出现肺泡化，14 d 肺泡化成熟，高氧组出现肺泡发育阻滞、肺纤维化，KGF 干预组肺纤维化不明显。与空气组比较，高氧组肺组织 TGF-β1蛋白表达在7、14 d 明显升高（9.43±0.64比8.62±0.52，P ﹤0.05；9.97±0.49比8.66±0.48，P ﹤0.01），差异有统计学意义，与空气组比较，KGF 干预组 TGF-β1蛋白表达各时间点差异无统计学意义（8.67±0.55比8.56±0.43，8.77±0.52比8.62±0.52，8.81±0.47比8.66±0.48，P 均﹥0.05）。与高氧组比较，KGF 干预组 TGFβ1蛋白表达在7 d、14 d 明显降低，差异有统计学意义（P 均﹤0.05）。结论 KGF 能抑制高氧暴露大鼠肺组织 TGF-β1蛋白的过度表达，减轻肺纤维化，这可能是 KGF 对高氧肺损伤的保护机制之一。

Objective To explore the effect of keratinocyte growth factor（KGF）on the lung tissue and expres-sion of transforming growth factor - β1（TGF - β1 ）in newborn rats with hyperoxia. Methods The 108 newborn SD rats were randomly divided into air group,hyperoxia group and KGF intervention group,and each group had 36 rats. The rats in every group were randomly divided into the 3,7,14 days subgroups,and each group had 12 rats. The rats in the hy-peroxia group and KGF intervention group were continually exposed to more than 950 mL/ L of oxygen box until the end of the experiment. KGF intervention group simultaneously undertook oxygen inhalation,hypodermic injection of 1 mg/ d recombinant human KGF（rhKGF）on the back on the first 3 days and 0. 5 mg/ d 3 days later till the end of the experi-ment. Air group and hyperoxia group were offered equivalent 9 g/ L saline. The rats in the air group took air. The sub -groups of the 3,7 and 14 days were cut for lung tissue in the corresponding time,observing lung tissue by light micro-scope for pathological changes and TGF - β1 protein expressed in the lungs was determined by immunohistochemistry. Results Air group sprout pulmonary alveolus on the 7th day,and the alveolaration finished on the 14th day,while hy-peroxia group had alveolar growth retardation and pulmonary fibrosis,but pulmonary fibrosis was not obvious in KGF in-tervention group. There was a significant difference on 7th day and 14th day between hyperoxia group and air group in TGF - β1（9. 43 ± 0. 64 vs 8. 62 ± 0. 52,P ﹤ 0. 05;9. 97 ± 0. 49 vs 8. 66 ± 0. 48,P ﹤ 0. 01）. There was no significant difference between KGF intervention group and air group in TGF - β1（8. 67 ± 0. 55 vs 8. 56 ± 0. 43,8. 77 ± 0. 52 vs 8. 62 ± 0. 52,8. 81 ± 0. 47 vs 8. 66 ± 0. 48,all P ﹥ 0. 05）. There＆#39;s a significant difference on 7th day and 14th day be-tween hyperoxia group and KGF intervention group in TGF - β1（all P ﹤ 0. 05）. Conclusions KGF can inhibit the pro-tein expression of TGF - β1 ,and this may be one of the possible mechanism underlying the protective effect of KGF a-gainst lung injury.