地塞米松和倍他米松对大鼠胎肺骨形态发生蛋白信号转导的影响

Effects of antenatal administration of dexamethasone and betamethasone on signal transduction of bone morphogenetic protein in the fetal lungs of rats

摘要:

目的：比较产前地塞米松、倍他米松给药对大鼠胎肺骨形态发生蛋白(BMP)信号转导通路的影响。方法：15只孕鼠随机分成5组：对照组、地塞米松治疗1 d组、3 d组和倍他米松治疗1 d组及3 d组。孕鼠妊娠第19天剖腹取胎鼠肺组织，通过RT-PCR、免疫组化和Western blot技术检测各组胎肺BMP4、BMP受体2（BMPR-II）、Smad1、转录活化因子2（ATF-2）基因转录及蛋白表达水平。结果：(1) BMP4 mRNA、BMPR-II mRNA、Smad1 mRNA的表达在倍他米松3 d组、1 d组及地塞米松3 d组均高于对照组(P＜0.05)。(2)免疫组化结果显示：与对照组相比，BMP4、BMPR-II、pSmad1、ATF-2在地塞米松3 d组、倍他米松1 d组及3 d组表达量显著增加(P＜0.01)。(3) Western blot检测显示与对照组相比，BMP4、BMPR-II蛋白在地塞米松3 d组及倍他米松1 d组、3 d组中表达丰富(P＜0.01)。结论：倍他米松、地塞米松可能参与调控大鼠胎肺BMP信号转导过程。对BMP信号转导分子BMP4、BMPR-II、Smad1表达的上调可能是其促胎肺成熟的重要机制之一。［中国当代儿科杂志，2010，12(11)：891-896］

Abstract:

OBJECTIVE: To study the role of antenatal glucocorticoid (dexamethasone and betamethasone) on bone morphogenetic protein (BMP) signal transduction of the rat fetal lungs. METHODS: Fifteen pregnant rats were randomly divided into five groups: the rats treated with dexamethasone for 1 day (1D-DEX) or 3 days (3D-DEX), with betamethasone for 1 day (1D-BEX) or 3 days (3D-BEX) or with normal saline (control group), followed cesarean section on the 19th day of gestation. The mRNA levels of BMP4, BMPR-II, Smad1 and ATF-2 of fetal rat lungs were ascertained by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of BMP4, BMPR-II, Smad1 and ATF-2 antigen expression in fetal lungs was assessed by immune histochemical staining. The expression of BMP4 and BMPR-II was determined by Western blot. RESULTS: The levels of BMP4, BMPR-II and Smad1 mRNA expression were up-regulated in the 1D-BEX, 3D-BEX and 3D-DEX groups compared with those in the control group (P＜0.05). The immune histochemiscal analysis showed that the expression of BMP4, BMPR-II, Phospho-Smad1 (pSmad1) and ATF-2 in the 1D-BEX, 3D-BEX and 3D-DEX groups was significantly higher than that in the control group (P＜0.01). The results of Western blot demonstrated that the expression of BMP4 and BMPR-II protein increased significantly in the 1D-BEX, 3D-BEX and 3D-DEX groups when compared with the control group (P＜0.01). CONCLUSIONS: Betamethasone and dexamethasone may play important roles in the regulation of BMP signal transduction in the rat fetal lungs. Up-regulation of BMP4, BMPR-II and Smad1 might be one of crucial factors for the glucocorticoid-induced maturity of fetal lungs.［Chin J Contemp Pediatr, 2010, 12 (11):891-896］