PDF(1274 KB)
PDF(1274 KB)
PDF(1274 KB)
高氧致新生鼠慢性肺疾病HoxB5 SPC AQP5表达及其意义
Expression of HoxB5, SPC and AQP5 in neonatal rats with hyperoxia-induced chronic lung disease
目的：肺泡上皮损伤是慢性肺疾病（CLD）主要病理改变之一，HoxB5基因是在肺发育过程中表达强烈的基因之一。该文探讨高浓度氧致新生鼠肺损伤时肺泡上皮损伤及修复能力，研究HoxB5在这一损伤中的动态表达规律及其与前者的关系。方法：建立高氧诱导新生鼠CLD模型, 80只早产鼠被随机分为实验组及对照组,分别应用免疫组化及RT-PCR技术测定肺组织HoxB5，SPC，AQP5蛋白及mRNA表达。结果：实验组肺组织HoxB5表达7 d后逐渐减少；高氧肺损伤SPC 3 d表达明显减少，7 d后开始增多，14 d、21 d明显高于对照组；而AQP5随着肺损伤加重表达量进行性下降。结论：高氧肺损伤新生鼠肺泡上皮细胞损伤明显，根据SPC，AQP5表达结果提示I型肺泡上皮细胞（AECI）损伤更甚且未得到正常修复，II型肺泡上皮细胞（AECII）虽然数量有所增加但其分化转化能力明显下降，而 HoxB5表达量减少可能致使大量的AECII失去了分化为AECI的功能。［中国当代儿科杂志，2009，11（1）：51-55］
OBJECTIVE: Alveolar epithelium impairment is one of pathological changes associated with chronic lung disease (CLD). Hoxb5 is one of the few homeobox genes strongly expressed in the developing lung. This study investigated the expression of HoxB5, SPC and AQP5 in rats with CLD in order to explore the role of Hoxb-5 in impairment and reparation of alveolar epithelium. METHODS: Eighty neonatal rats were randomly exposed to hyperoxia (model group ) or to room air (control group) (n=40 each). The CLD model was induced by hyperoxia exposure. The expression of HoxB5, SPC and AQP5 protein and mRNA in the lung tissue was detected by immunohistochemistry and RT-PCR 1, 3, 7, 14 and 21 days after exposure. RESULTS: In the model group HoxB5 expression significantly decreased 7, 14 and 21 days after hyperoxia exposure. SPC expression decreased 3 days after hyperoxia exposure but increased significantly 7, 14 and 21 days after hyperoxia exposure as compared to the control group. AQP5 expression was progressively reduced with prolonged hyperoxia exposure. CONCLUSONS: Hyperoxia exposure may lead to alveolar epithelial cell (AEC) damage in neonatal rats. The increased SPC expression and decreased AQP5 expression suggested that the ability of differentiation and transformation of AECII into AECI decreased in neonatal rats with CLD. The decreased HoxB5 expression following hyperoxia exposure might contribute to a decreased ability of differentiation of AECII.［Chin J Contemp Pediatr, 2009, 11 (1):51-55］
HoxB5 / SPC / AQP5 / 慢性肺疾病 / 肺泡上皮细胞 / 大鼠
HoxB5 / SPC / AQP5 / Chronic lung disease / Alveolar epithelial cell / Rats
［1］Gehring WJ, Affolter M, Bürglin T. Homeodomain proteins［J］. Annu Rev Biochem, 1994, 63:487-526.
［2］Manzanares M, Wada H, Itasaki N, Trainor PA, Krumlauf R, Holland PW. Conservation and elaboration of Hox gene regulation during evolution of the vertebrate head［J］. Nature, 2000, 408(6814):854-857.
［3］Golpon HA, Geraci MW, Moore MD, Miller HL, Miller GJ, Tuder RM, et al. HOX Genes in human lung:altered expression in primary pulmonary hypertension and emphysema［J］.Am J Pathol, 2001, 158(3):955-966.
［4］Volpe MV, Martin A, Vosatka RJ, Mazzoni CL, Nielsen HC. Hoxb-5 expression in the developing mouse lung suggests a role in branching morphogenesis and epithelial cell fate［J］. Histochem Cell Biol, 1997, 108(6):495-504.
［5］Rottier R, Tibboel D. Fetal lung and diaphragm development in congenital diaphragmatic hernia［J］. Semin Perinatol, 2005, 29(2):86-93.
［6］Crapo JD, Barry BE, Gehr M. Cell number and cell characteristics of the normal human lung［J］. Am Rev Resp, 1982, 126(2):332-337.
［7］Lesur O, Arsalane K. Lung alveolar epithelial cell migration in vitro: modulators and regulation processes［J］. Am J Physiol, 1996, 370(3 Pt 1):311-319.
［8］Souza P, Tanswell AK, Post M. Different roles for PDGF-alpha and-beta receptors in embryonic lung development［J］. Am J Respir Cell Mol Biol, 1996, 15(4):551-562.
［9］Nielsen HC, Martin A, Volpe MV, Hutzis D, Vosatka RJ. Grow-th factor control of growth and epithelial differentiationin embryonic lungs［J］. Biochem Mol Med, 1997, 60(1):38-48.
［10］Zhao JJ, Lazzarini RA, Pick L. The mouse Hox 1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene［J］. Genes Dev, 1993, 7(3):343-354.
［11］Wu Q, Lothe RA, Ahlquist T, Silins I, Tropé CG, Micci F, et al. DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9,HOXB5,SCGB3A1,and CRABP1 as novel targets［J］. Molecular Cancer, 2007, 6:45.
［12］Hershko AY, Kafri1 T, Fainsod A, Razin A. Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse development［J］. Gene, 2003, 302(1-2):65-72.
