Nonlinear imaging study of extracellular matrix in chemical-induced, developmental dissecting aortic aneurysm: evidence for defective collagen type III.
Nonlinear imaging study of extracellular matrix in chemical-induced, developmental dissecting aortic aneurysm: evidence for defective collagen type III.
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DOI：
10.1002/bdra.20408
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
B. Gong;Ju Sun;Gracie Vargas;Q. Chang;Ya Xu;D. Srivastava;P. Boor
中科院分区：
文献类型：
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作者：
B. Gong;Ju Sun;Gracie Vargas;Q. Chang;Ya Xu;D. Srivastava;P. Boor
背景：在最近建立的子宫内暴露于氨基脲的夹层动脉瘤模型上，我们使用标准方法和两种非线性成像技术，即多光子荧光(MPF)和二次谐波(SHG)显微镜，对弹性蛋白和胶原进行了检测。方法给SD大鼠灌胃氨基脲(6.13 mg/kg/d)。妊娠14~20天(GD14~20)。分别于出生后第1天(PND1)、第7天和第28天(PND1、PND7和PND28)采集GD20的胎儿和仔鼠；对照组来自用生理盐水处理过的母鼠。在激发波长为800 nm的MPF和倍频显微镜下观察主动脉免疫组织病理学和胶原/弹性蛋白信号强度。结果GD20胎鼠出生时，几乎100%发生了巨大的主动脉弓DAA(即，GD20胎儿无病变)。MPF和SHG显示胶原蛋白在GD20和新生儿中显著降解，但在PND28时恢复正常。免疫印迹和免疫组织化学结果显示，GD20胎儿和新生仔鼠合并的主动脉内膜和外膜III型胶原含量降低。在7日龄和28日龄幼鼠中，血管中膜DAA血的溶解和可染色的III型胶原的恢复。在愈合的DAA(PND28只仔鼠)中，弹性蛋白局灶性排列紊乱。结论MPF和SHG显微镜可提供有关主动脉弹性蛋白和胶原的敏感和高分辨率信息。在这个DAA模型中，胶原显示异常的成像质量，可能与发育中的细胞外基质中III型胶原的显著减少有关。出生缺陷研究(A部分)2008年。
BACKGROUND Using a recent model of dissecting aortic aneurysm (DAA) caused by in utero exposure to semicarbazide, we examined the elastin and collagen using standard methods and two nonlinear imaging techniques, multiphoton fluorescence (MPF) and second harmonic generation (SHG) microscopy. METHODS Sprague-Dawley rat dams were given semicarbazide (6.13 mg/kg/day i.p.) from gestational days 14 to 20 (GD14-20). Fetuses were harvested on GD20 and pups on postnatal day 1 (PND1), PND7, and PND28; matched controls were from dams treated with saline. Aortic immunohistopathology and collagen/elastin signal intensity via MPF and SHG microscopy at an excitation wavelength of 800 nm were studied. RESULTS Massive DAA of the aortic arch occurred in nearly 100% of pups at birth (i.e., no GD20 fetuses showed lesions). MPF and SHG demonstrated that collagen was significantly degraded at GD20 and in newborns, but normalized by PND28. GD20 fetuses and newborn pups showed a decreased content of medial and adventitial collagen type III in pooled aortas by Western blot and immunohistochemistry. In 7- and 28-day-old pups resolution of DAA blood in vascular media and a recovery of stainable collagen type III was found. Elastin in healed DAA (PND28 pups) was focally disorganized. CONCLUSION MPF and SHG microscopy provide sensitive and high-resolution information on aortic elastin and collagen. In this model of DAA, collagen displays aberrant imaging quality likely linked to a marked decrease in collagen type III in the developing extracellular matrix. Birth Defects Research (Part A) 2008.