表皮生长因子对新生未成熟大鼠高氧性损伤肺组织纤维化的影响

The effect of Epidermal Growth Factor on the pulmonary fibrosis of neonatal premature rats exposed to hyperoxia

目的 探讨外源性表皮生长因子（epidermal growth factor，EGF）对新生大鼠高氧性损伤肺组织纤维化的影响。方法 取胎龄21d剖宫产出生的新生Sprague-dawley（SD）大鼠持续吸入95％的O2制作未成熟肺高氧性损伤模型，随机分为高氧＋EGF组和高氧＋生理盐水（NS）组，另设空气＋NS对照组；所有组按给药（或NS）时间分为3个亚组，即：a亚组（1—3d）、b亚组（4～6d）、c亚组（1～6d）；各亚组均于生后3、7、14d分批处死采取肺组织标本。应用Masson三色染色、纤维化评分及羟脯氨酸含量测定判断肺组织纤维化的程度。结果 空气＋NS组未见胶原沉积增多现象，高氧＋NS组生后7d胶原沉积明显增多，14d程度加重，7、14d高氧＋EGF组较高氧＋NS组胶原沉积明显减少；羟脯氨酸（HYP）的含量和纤维化评分也表明7、14d时高氧＋EGF组胶原纤维的含量较高氧＋NS组明显减少（P〈0．01）；在高氧＋EGF组中b亚组效果不及a亚组和c亚组。结论 表皮生长因子可以减轻新生未成熟大鼠高氧性损伤肺组织纤维化程度，在肺损伤早期应用效果更好。

Objective To study the effect of Epidermal Growth Factor （EGF） on the fibrosis of the injured lung tissue of neonatal premature rats exposed to hyperoxia. Methods The neonatal Sprague-Dawley rats of 21-day gestational age were selected and exposed to 95% oxygen continuously to induced hyperoxic lung injury. The model rats were divided into two groups randomly, EGF trail group and normal saline （NS） control group. The untreated rats were taken into the air plus normal saline control group. Each group was divided into three subgroups： group a （1-3 day）, group b （4-6 day） and group c （1-6 day） according to treatment duration of EGF or NS. The rats in each subgroups were sacrificed and their lung tis- sues were harvested at day 3, 7 and 14. The lung tissue was stained by Masson tfichrome method, the degree of pulmonary fibrosis was evaluated by fibrosis score and hydroxyproline content. Results Masson tfichrome stain showed that pulmonary fibrosis emerged in hyperoxic NS group at postnatal day 7 and aggravated until day 14. Collagen fibers deposition, fibrosis score and hydroxyproline content in EGF groups were lower than that of NS control group at day 7 and day 14 in hyperoxic environment（P 〈0. 01）. The therapeutic effect of subgroup b was not as effective as subgroup a or c. Conclusions Early use of EGF can decrease the severity of the pulmonary fibrosis of neonatal premature rats exposed to hyperoxia.