Adriamycin induces notochord hypertrophy with conservation of sonic hedgehog expression in abnormal ectopic notochord in the adriamycin rat model
Adriamycin induces notochord hypertrophy with conservation of sonic hedgehog expression in abnormal ectopic notochord in the adriamycin rat model
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DOI：
10.1016/j.jpedsurg.2004.02.040
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发表时间：
2004-06-01
影响因子：
2.4
通讯作者：
Puri, P
中科院分区：
文献类型：
--
作者：
Mortell, A;O'Donnell, AM;Puri, P
背景/目的：阿霉素大鼠模型（ARM）是脊椎、肛门直肠、心脏、气管食管、肾脏、肢体（VEGIL）联合的成熟模型。表达Sonic Hedgehog（Shh）的脊索在ARM胚胎的前肠区域严重畸形，出现腹侧异位分支。作者设计了这项研究来验证这一假设，即表达Shh的异位脊索可能有助于脊索体积相对于总胚胎体积的增加，从而导致受影响胚胎脊索中Shh浓度的增加。在妊娠第7天（E7）、E8和E9对大鼠腹腔内给予阿霉素，对照动物给予生理盐水。E12和E14的胚胎回收的Shh的表达进行了化学检测，使用Cavalieri技术进行定量形态学，以确定胚胎和脊索volume.Results：胚胎阿霉素和对照组在E12和E14显示在脊索的Shh表达水平相当的所有位置。与同等controls.Conclusions相比，阿霉素胚胎在E12和E14时每个胚胎的脊索百分比显著增加：这些数据表明，阿霉素诱导脊索肥大。由于脊索的所有区域都分泌Shh，这可能导致Shh在前肠异常附近的浓度梯度更高，可能导致VEGIL联合中发现的畸形。(C)2004年爱思唯尔公司All rights reserved.
Background/Purpose: The Adriamycin rat model (ARM) is a well-established model of the Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, Limb (VACTERL) association. The notochord, which expresses Sonic Hedgehog (Shh), has been found to be grossly malformed with ventral ectopic branches in the foregut region of embryos in the ARM. The authors designed this study to test the hypothesis that Shh-expressing ectopic notochord could contribute to an increased volume of notochord relative to total embryo volume, resulting in an increased concentration of Shh in the notochord of affected embryos.Methods: Adriamycin was administered intraperitoneally to rats on days 7 (E7), E8, and E9 of gestation and saline to control animals. Embryos recovered at E12 and E14 were examined immunohistochemically for Shh expression, Quantitative morphology using the Cavalieri technique was performed to determine embryo and notochord volume.Results: Embryos in both Adriamycin and control groups at E12 and E14 showed comparable levels of Shh expression in notochord at all locations. The percentage of notochord per embryo was significantly increased in Adriamycin embryos at E12 and E14 compared with equivalent controls.Conclusions: These data suggest that Adriamycin induces notochord hypertrophy. With all regions of the notochord secreting Shh, this could result in a higher concentration gradient of Shh in close abnormal proximity to the foregut, possibly contributing to the malformations found in the VACTERL association. (C) 2004 Elsevier Inc. All rights reserved.