角质细胞生长因子对吸入高体积分数氧新生大鼠肺组织的影响

Effect of Keratinocyte Growth Factor on Lung Tissue in Newborn Rats with Hyperoxia Inhalation

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结构的影响。方法将新生的108只SD大鼠随机分为空气组、高氧组和KGF干预组,每组36只。每组又分为3 d、7 d、14 d 3个亚组。高氧组、KGF干预组大鼠持续暴露于氧体积分数>950 mL.L-1氧箱中,KGF干预组于吸氧同时背部皮下注射重组人角质细胞生长因子(rhKGF)1 mg.d-1,连用3 d后改为0.5 mg.d-1直至实验结束。空气组和高氧组给予等量9 g.L-1盐水。空气组大鼠呼吸空气。3 d、7 d、14 d亚组在相应时间点取肺组织,通过肉眼及光镜下观察其肺组织病理学变化,并作肺泡辐射状计数(RAC)。结果空气组7 d时出现肺泡化,14 d时肺泡化成熟。高氧组时小血管扩张充血,肺间质细胞增多,7 d时肺间隔变厚,肺泡腔大小不一,肺泡数减少,14 d时肺泡数明显减少,肺泡大小不等,出现明显纤维化。KGF干预组7 d时可见肺泡结构较完整,14 d时少数肺泡融合,间质细胞增生不严重。高氧组3 d时RAC与空气组相比差异无统计学意义(P>0.05),7 d、14 d时RAC与空气组相比差异均有统计学意义(Pa>0.01)。KGF干预组各时间点RAC与空气组比较差异均无统计学意义(Pa>0.05)。结论长时间暴露于高氧环境,可导致新生大鼠肺组织发育障碍,但KGF能促进肺泡的发育,减轻纤维化,可有效减轻高氧吸入对新生大鼠肺组织的损伤。

Objective To explore the effect of keratinocyte growth factor（KGF） on lung tissue structure in newborn rats with hyperoxia inhalation. Methods The 108 newborn SD rats were randomly divided into air group,hyperoxia group and KGF intervention group.Each group had 36 rats.The rats in every group were randomly into the 3rd,7th,14th day subgroups,respectively.Rats in hyperoxia group and KGF intervention group were continually exposed to more than 950 mL·L-1 of the oxygen box until the end of the experiment.KGF intervention group simultaneously undertook oxygen inhalation,hypodermic injection of 1 mg·d-1 rhKGF on the back at the first 3 days and 0.5 mg·d-1 3 days later until the end of the experiment.Air group and hyperoxia group were offered equivalent NS.These rats in air group took air.The sub-groups of the 3th,7th and 14th were cut lung tissue in the corresponding of time,observing lung tissue by light microscope for pathological changes and radial alveolar count（RAC）. Results Air group sprout pulmonary alveolus on the 7th day,and the alveolaration finished on the 14th day.Minute vessel came out hemangiectasis and hyperaemia,and the pulmonary interstitial cells increased after exploring to hyperxia for 3rd days in hyperoxia group;the pulmonary gap became thicker,the size of alveolus varied and its number reduced in the 7th day of hyperoxia group;while in the 14th day of hyperoxia group,the number of pulmonary alveolus obviously reduced and their sizes were different,and fibrosis appeared.The structure of pulmonary alveolus was completed in the 7th day of KGF intervention group,fusion of pulmonary alveoli was few and the proliferation of interstitial cell was not very serious in the 14th day.There was no significant difference between the 3rd day of hyperoxia group and air group on RAC（P0.05）.There was a significant difference in the 7th and 14th day between hyperoxia group and air group on RAC（Pa0.01）.There was no significant difference between KGF intervention group and air group on RAC at any times（Pa0.05）. Conclusions Long-terms of exposure to hyperoxia may result in pulmonary tissue′s growth impediment,while KGF can promote pulmonary alveolus′s growth and reduce fibrosis.KGF can effectively reduce the newborn rats′ lung damage caused by hyperoxia.