胰岛素样生长因子结合蛋白2在新生鼠肺发育中的作用

Role of Insulin-like Growth Factor Binding Protein-2 During Lung Development in Newborn Rats

目的探索胰岛素样生长因子结合蛋白(IGFBP)2在新生鼠肺发育中的作用。方法SD孕鼠80只分为4组,即A:对照组;B:地塞米松(Dex)1组;C:Dex2组;D:维A酸(RA)组。A、B、D组分别于孕18～20d皮下注射生理盐水、Dex,腹腔注射RA;C组于生后1～3d皮下注射Dex。各组分别于孕18、20、21d(C组孕期不取)、生后1、3、5、7、10、14、21d取肺标本作形态学检查、免疫组织化学、Westernblot及RT PCR检测。结果1.肺组织形态学:B、C组早期肺泡发育提前,数目多,壁薄,晚期则明显落后于A、D组。2.IGFBP2肺表达:A组中IGFBP2主要在胎肺组织中表达,孕18d左右表达最强,随后表达渐减弱。B、C组表达趋势同A组,但生后各时间点均较A组增强;D组生后各时间点均较A组减弱。3.Westernblot:IGFBP2多肽表达强度各组孕18d表达最强,随后渐降低;B、C组生后各时间点表达强度明显高于A组(P均<0.01);D组各时间点浓度均明显低于A组(P均<0.01)。4.RT PCR:IGFBP2mRNA表达的强度变化规律与其肽浓度变化相似。结论IGFBP2在肺发育过程起重要作用,其浓度过高则影响肺发育。

Objective To explore the role of insulin-like growth factor binding protein (IGFBP)-2 during lung development inneonates.Methods Eighty timed pregnant Sprague-Dawley(SD)rats were randomly divided into 4 groups.group A:control group,20 rats were injected subcutaneously (sc) with normal saline during gestation ages on 16 to 18 days;group B:dexamethasone (Dex) 1 group,20 rats were injected sc with Dex [0.5 mg/(kg·d)] at the same time as above;group C:Dex 2 group,all newborn rats were injected sc with Dex(25 μg/d) on 1 to 3 days;group D:retinoic acid (RA) group,the pregnant rats were injected intraperitoneally with all trans-RA[500 μg/(kg·d)] at the same time as Group A.The collection of lung tissue was obtained at the following ages:fetuses of gestational ages 18,20 and 21 days,and after birth at 1,3,5,7,10,14 and 21 days.Lung tissues were used for histopathology,the polypeptides analysis of IGFBP-2 (immunohistochemistry and western blot) and mRNA analysis (RT-PCR).Results The strongest expressions of IGFBP-2 in all groups occurred on 18th day of gestation,then were gradually weakened to trace.Compared with group A, the expression quantity after birth in groups B and C were significantly high(P<0.01),but significantly lower in group D(P< 0.01).Relative abundance of IGFBP-2 mRNA in 4 groups was similar to the expression of their polypeptides.Conclusions IGFBP-2 plays an important role during lung development.The development and maturity of lungs will be influenced by the superabundant expression of IGFBP-2.