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

陈筱青; 吴升华; 周晓玉

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中国当代儿科杂志 ›› 2010, Vol. 12 ›› Issue (11) : 891-896.

论著·实验研究

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

陈筱青，吴升华，周晓玉

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

CHEN Xiao-Qing, WU Sheng-Hua, ZHOU Xiao-Yu

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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］

导出引用

陈筱青, 吴升华, 周晓玉. 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[J]. 中国当代儿科杂志. 2010, 12(11): 891-896

CHEN Xiao-Qing, WU Sheng-Hua, ZHOU Xiao-Yu. Effects of antenatal administration of dexamethasone and betamethasone on signal transduction of bone morphogenetic protein in the fetal lungs of rats[J]. Chinese Journal of Contemporary Pediatrics. 2010, 12(11): 891-896

中图分类号： R-33

参考文献

［1］Crowther CA, Haslam RR, Hiller JE, Doyle LW, Robinson JS. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial［J］. Lancet, 2006, 367(9526):1913-1919.
［2］Pongracz JE, Stockley RA. Wnt signalling in lung development and diseases［J］. Respir Res, 2006, 7(1):15.
［3］Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins［J］. Growth Factors, 2004, 22(4):233-241.
［4］Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-β family signalling［J］. Nature, 2003, 425(6958): 577-584.
［5］Warburton D, Bellusci S, De Langhe S, Del Moral PM, Fleury V, Mailleux A, et al. Molecular mechanisms of early lung specification and branching morphogenesis［J］. Pediatr Res, 2005, 57(5):26-37.
［6］Sebald W, Nickel J, Zhang JL, Mueller TD. Molecular recognition in bone morphogenetic protein (BMP)/receptor interaction［J］. Biol Chem, 2004, 385(8):697-710.
［7］阚清，周晓玉，顾筱琪，刘茹，郭锡熔．盐酸氨溴索、地塞米松产前用药对大鼠胎肺形态发育影响的对比［J］. 实用儿科临床杂志, 2007, 22(14):1050-1052.
［8］陈筱青，周晓玉，阚清，郭锡熔. 地塞米松与倍他米松对大鼠胎肺形态发育影响的对比［J］. 中华围产医学杂志，2009, 12(1):36-40.
［9］Eblaghie MC, Reedy M, Oliver T, Mishina Y, Hogan Bl. Evidence that autocrine signaling through Bmpr1a regulates the proliferation,survival and morphogenetic behavior of distal lung epithelial cells［J］. Dev Biol, 2006, 291(1):67-82.
［10］Beppu H, Kawabata M, Hamamoto T, Chtil A, Minowa O, Noda T, et al. BMP type II receptor is required for gastrulation and early development of mouse embryos［J］. Dev Biol, 2000, 221(1):249-258.
［11］Chen C, Chen H, Sun J, Bringas P Jr, Chen Y, Warburton D, et al. Smad1 expression and function during mouse embryonic lung branching morphogenesis［J］. Am J Physiol Lung Cell Mol Physiol, 2005, 288(6):1033-1039.
［12］Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis［J］. Gene, 2001, 273(1):1-11.
［13］Joyce DA,Gimblett G, Steer JH. Targets of glucocorticoid action on TNF-α release by macrophages［J］. Inflamm Res, 2001, 50(7):337-340.
［14］Monzen K, Hiroi Y, Kudoh S, Akazawab H, Okaa T, Takimotoa E, et al. Smads, TAK1, and their common target ATF-2 play a critical role in cardiomyocyte differentiation［J］. J Cell Biol, 2001,153(4):687-698.