在阿霉素大鼠模型中，发育中胚胎纤连蛋白表达增加与脊索异常有关。
Increased fibronectin expression in developing embryos is associated with abnormal notochord in the Adriamycin rat model.
作者信息
Mortell A, O'Donnell A M, Giles S, Bannigan J, Puri P
机构信息
The Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.
出版信息
Pediatr Surg Int. 2004 Apr;20(4):276-82. doi: 10.1007/s00383-003-1126-y. Epub 2004 Feb 18.
BACKGROUND
The VACTERL association is a spectrum of clinical conditions, including esophageal atresia (EA) and tracheoesophageal fistula (TEF), which affects approximately 1 in 5,000 live human births. The administration of intraperitoneal Adriamycin to pregnant rats reliably induces anomalies, such as EA and TEF, in their offspring, in what is known as the Adriamycin rat model (ARM). In affected embryos the presence of gross notochord abnormalities is commonly found, with typical features being ectopic ventral branches and adherence of the notochord to the foregut. Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein present on most cell surfaces, in extracellular fluids and in plasma. FN is involved in various functions, including cell adhesion, cell motility and wound healing. Previous studies in rats have shown that a single dose of Adriamycin can produce an appreciable rise in FN levels in various organs such as kidney and heart. We hypothesised that Adriamycin administration could promote upregulation of FN expression contributing to increased gut-notochord adherence and the development of abnormal ventral notochordal branching in the ARM. This study was designed to investigate FN expression in ARM embryos.
METHODS
Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats on days 7,8 and 9 of gestation (E7, E8 and E9 respectively). Control animals were given saline. Embryos recovered on E10-E14 were fixed, embedded in paraffin and sectioned. Immunohistochemistry using an anti-FN rabbit polyclonal antibody was performed.
RESULTS
FN expression in both Adriamycin and control embryos on E10, E11 and E12 was comparable. However, the levels of FN expression in Adriamycin embryos on E13 and E14 were significantly greater in embryos with abnormal notochords than in equivalent control embryos.
CONCLUSION
Adriamycin-induced increased expression of FN, in the ARM, may contribute to abnormal notochord development leading to the VACTERL association.
背景
VACTERL 综合征是一系列临床病症，包括食管闭锁（EA）和气管食管瘘（TEF），在每 5000 例活产人类婴儿中约有 1 例受其影响。给怀孕大鼠腹腔注射阿霉素可在其后代中可靠地诱发诸如 EA 和 TEF 等异常，即所谓的阿霉素大鼠模型（ARM）。在受影响的胚胎中，通常会发现明显的脊索异常，典型特征是异位腹侧分支以及脊索与前肠粘连。纤连蛋白（FN）是一种细胞外基质（ECM）糖蛋白，存在于大多数细胞表面、细胞外液和血浆中。FN 参与多种功能，包括细胞黏附、细胞运动和伤口愈合。先前在大鼠中的研究表明，单剂量阿霉素可使肾脏和心脏等各种器官中的 FN 水平显著升高。我们推测，在 ARM 中，阿霉素给药可促进 FN 表达上调，导致肠 - 脊索粘连增加以及异常腹侧脊索分支的形成。本研究旨在调查 ARM 胚胎中 FN 的表达情况。
方法
在妊娠第 7、8 和 9 天（分别为 E7、E8 和 E9）给怀孕大鼠腹腔注射阿霉素（1.75 mg/kg）。对照动物注射生理盐水。在 E10 - E14 回收胚胎，固定、石蜡包埋并切片。使用抗 FN 兔多克隆抗体进行免疫组织化学检测。
结果
E10、E11 和 E12 时，阿霉素处理组和对照组胚胎中的 FN 表达相当。然而，E13 和 E14 时，脊索异常的阿霉素处理组胚胎中的 FN 表达水平显著高于相应的对照胚胎。
结论
在 ARM 中，阿霉素诱导的 FN 表达增加可能导致脊索发育异常，进而引发 VACTERL 综合征。
Zotero 插件