氨溴索和糖皮质激素对胎鼠肺组织骨形态发生蛋白4表达的影响

Effects of antenatal ambroxol and glucocorticoid on bone morphogenetic protein 4 in the fetal lung of rats

目的探讨产前给予氨溴索、糖皮质激素(地塞米松、倍他米松)对胎鼠肺组织骨形态发生蛋白4(BMP4)表达的影响。方法18只孕鼠随机分成6组:对照组、氨溴索组、地塞米松1d组和3 d组,倍他米松1 d组和3 d组,每组3只。孕鼠妊娠第19天行剖宫产取胎仔肺组织,通过逆转录聚合酶链反应、免疫组化和免疫印记技术检测各组胎肺BMP4基因转录水平及蛋白表达差异。结果BMP4 mRNA表达在地塞米松3 d组、倍他米松1、3 d组的表达均明显高于对照组(P<0.05),氨溴索组与地塞米松1 d组与对照组相比差异无统计学意义(P>0.05)。免疫组化和免疫印记法结果显示,与对照组相比,地塞米松3 d组、倍他米松1 d组及3 d组BMP4表达量显著增加(P<0.01),而氨溴索组、地塞米松1 d组与对照组相比表达差异无统计学意义(P>0.05)。结论产前给予地塞米松、倍他米松均能显著促进胎肺组织BMP4的表达,提示糖皮质激素可能通过上调BMP4表达促进大鼠胎肺发育。

Objective To investigate the role of antenatal ambroxol and glucocorticoid （dexamethasone and betamethasone） on bone morphogenetie protein 4 （BMP4） of the rat fetal lung. Methods Eighteen pregnant rats were randomly assigned into six groups with 3 rats in each group： rats treated with ambroxol, 1-day dexamethasone （1D-DEX）, 1-day betamethasone （1D-BEX）, 3-day dexamethasone （3 D-DEX）, 3-day betamethasone （ 3 D-BEX） and saline （ controls ） antenatal, followed cesarean section on the 19^th day of gestation. The mRNA level of BMP4 of 6 fetal rat lungs in each pregnant rat were analyzed by reverse transcriptase polymerase chain reaction （RT-PCR）. The expression of BMP4 antigen expression in embryo lung were assessed by immunohistochemistry stain. The expression of BMP4 were detected by Western blotting. Results BMP4 mRNA expression was up-regulated in the rats treated with 1D-BEX, 3D-BEX and 3D-DEX compared with controls （P 〈 0. 05 ）. No significant difference was found in the 1D-DEX and ambroxol treated rats compared with the controls （P 〉 0. 05 ）. Results of the immunohistochemistry and Western blotting demonstrated that the expression of BMP4 protein was significantly increased in the 1D-BEX, 3D-BEX and 3D-DEX treated animals （P 〈 0. 01 ）. While no change could be found in the fetal lung of ambroxol and 1D-DEX treated anmimals. The BMP4 protein levels in ambroxol and 1D-DEX treated animals were not notably difference compared with that of controls （P 〉 0. 05 ）. Conclusion Betamethasone and dexamethasone may promote the expression of BMP4 in the rat fetal lung. Up-regulation of BMP4 might be one of critical factor for the glucocorticoidinduced development of fetal lung.