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目的:探讨长期应用糖皮质激素(ICSs)对新生大鼠肺形态结构及其对肺内胰岛素样生长因子结合蛋白2(IGFBP-2)表达的影响。方法:新生SD大鼠48只随机分为3组:对照(CONT)组(雾化吸入生理盐水);雾化吸入布地奈德(BUD)组;腹腔注射地塞米松(DEX)组。每个干预组内设7 d给药组与14 d给药组。大鼠5日龄时开始干预,各组在连续给药7、14d后,测量大鼠体重及肺组织重量,计算肺系数,通过肺组织形态学分析评估肺发育程度,应用蛋白免疫印迹技术(WB)检测IGFBP-2在肺组织中的表达。结果:①大鼠体重及肺系数:BUD组与CONT组体重间差异无统计学意义(P>0.05),但DEX组体重较CONT组明显下降(P<0.01)。BUD组肺系数低于CONT组(P<0.01)。给药14 d后,DEX组肺系数与CONT组间无统计学差异(P>0.05);②肺组织形态学:BUD组、DEX组肺泡囊数量较CONT组减少(P<0.01),间隔变薄(P<0.01),囊腔增大(P<0.05),BUD组、DEX组肺泡形态学指标间无统计学差异(P>0.05);③肺组织IGFBP-2蛋白表达:IGFBP-2在BUD组、DEX组表达强于CONT组。结论:长期应用糖皮质激素可抑制新生大鼠肺泡化过程,该现象可能与糖皮质激素上调IGFBP-2在肺组织中的表达有关。
Objective: To investigate the effect of long-term administration of glucocorticoid (ICSs) on lung morphology and the expression of insulin-like growth factor binding protein 2 (IGFBP-2) in neonatal rats. Methods: Forty-eight newborn Sprague-Dawley rats were randomly divided into 3 groups: control (CONT) group (nebulized normal saline), inhaled budesonide (BUD) group and dexamethasone (DEX) group. Each intervention group had 7 d administration group and 14 d administration group. The rats began to intervene at 5 days of age. After 7 and 14 days of continuous administration, the body weight and lung weight of rats were measured, and the lung coefficient was calculated. The lung development was evaluated by lung histomorphometry. Western blotting WB) to detect IGFBP-2 expression in lung tissue. Results: ① Body weight and lung coefficient of rats: There was no significant difference between BUD group and CONT group (P> 0.05). However, the body weight of DEX group was significantly lower than that of CONT group (P <0.01). The lung coefficient of BUD group was lower than that of CONT group (P <0.01). After 14 days of administration, the lung coefficient of DEX group was not significantly different from that of CONT group (P> 0.05). ② The morphology of lung tissue: The number of alveolar vesicles in BUD group and DEX group was lower than that in CONT group (P <0.01) There was no significant difference in alveolar morphology among BUD group and DEX group (P> 0.05). The expression of IGFBP-2 protein in lung tissue: BUD group, DEX group was stronger than CONT group. CONCLUSION: Long-term glucocorticoid treatment can inhibit the alveolar process of neonatal rats, which may be related to the up-regulation of IGFBP-2 expression in lungs by glucocorticoid.