维甲酸、血小板衍生生长因子对早产新生大鼠高浓度氧肺损伤的影响

Effect of retinoic acid and platelet derived growth factor on lung injury in hyperoxia-exposed premature rats

目的观察维甲酸（RA）和血小板衍生生长因子（PDGF）对高浓度氧（简称高氧）抑制早产新生大鼠肺发育的影响，探讨其作用机制。方法1日龄早产SD大鼠随机分为：空气＋生理盐水组（Ⅰ组）、高氧＋生理盐水组（Ⅱ组）、空气＋RA组（Ⅲ组）、高氧＋RA组（Ⅳ组）。Ⅱ、Ⅳ组持续暴露于85％氧气中。Ⅲ、Ⅳ组每目腹腔注射RA500μg／kg，Ⅰ、Ⅱ组注射相同剂量的生理盐水。应用RT—PCR和免疫组织化学法检测各时间点（生后4、7、10、14及21d）各组大鼠肺组织PDGFmRNA和蛋白表达水平。结果随日龄的增加，PDGF—A、-B mRNA及蛋白表达发生不同的变化。与Ⅰ组比较，高氧暴露下PDGF-B mRNA和蛋白表达显著增高（P〈0．05），但PDGF-A mRNA及蛋白表达却显著降低（P〈0．05）。RA上调PDGF—A mRNA及蛋白表达（P〈0．05），但对PDGF—B mRNA及蛋白表达作用不显著（P〉0．05）。结论高氧暴露下，PDGF—AmRNA及蛋白表达受抑，PDGF—BmRNA及蛋白表达增强。PDGF-A、-B共同参与了高氧暴露下肺组织损伤过程。RA上调PDGF—AmRNA及蛋白表达，能部分逆转高氧引起的肺损伤。

Objective To investigate temporal and spatial effective mechanism of retinoic acid （RA） and platelet derived growth factor（PDGF） on lung injury in hyperoxia-exposed premature rats. Methods One-day-old SD premature rats were randomly assigned to 4 groups： air ＋ NS group（Ⅰ）, O2 ＋ NS group（Ⅱ）, air ＋ RA group（Ⅲ）, O2 ＋ RA group（Ⅳ）. Group Ⅱ, Ⅳ were kept in chambers containing 85 % oxygen, the other two groups were exposed to air. Group Ⅲ, Ⅳ were intraperitoneally injected with RA[500 μg/（ kg·d）], group Ⅰ, Ⅱ were intraperitoneally given the same dose of saline. Reverse trarlscriptase polymerase chain reaction （RT-PCR） and immunohistochemical method were used to measure the expression levels of PDGF mRNA and protein at 4, 7, 10, 14 and 21 days after birth. Results With increase in days, the expression of PDGF-A,-B mRNA and protein changed differently. Compared with group Ⅰ, with prolonged hyperoxia exposure, the content of PDGF-B mRNA and protein increased significantly （P 〈 0.05 ）, but PDGF-A mRNA and protein reduced markedly （ P 〈 0.05 ）. RA upregulated PDGF-A mRNA and protein expression （ P 〈 0.05 ）, there was no influence on PDGF-B mRNA and protein expression. Conclusion When exposed to hyperoxia, the expression of PDGF-A mRNA and protein is inhibited, whereas PDGF-B mRNA and protein expression increase. Both PDGF-A and PDGF-B are involved in lung injury process induced by hyperoxia exposure. RA can upregulate PDGF-A mRNA and protein expression, which can partially reverse lung injury.