Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice
Ultrastructural morphometry of capillary basement membrane thickness in normal and transgenic diabetic mice
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DOI：
10.1002/ar.a.10038
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发表时间：
2003-04-01
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影响因子：
--
通讯作者：
Epstein, PN
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作者：
Carlson, EC;Audette, JL;Epstein, PN
毛细血管基底膜（CBM）增厚是糖尿病患者和糖尿病动物模型的超微结构标志。然而，取样的组织种类繁多，采用的方法也多种多样，这使得对厚度数据的解释变得困难。我们以前表明，OVE 26转基因糖尿病小鼠的非细胞肾小球BM增厚超过正常的年龄相关增厚，在目前的研究中，我们假设其他微血管BM同样会显示相对于年龄匹配的对照组增加的宽度。因此，从300-350日龄正常和转基因小鼠中收集一系列组织，包括骨骼肌和心肌、眼视网膜和脉络膜、外周神经、肺、胰腺和肾小球。通过毛细管壁的横截面的透射电子显微照片的制备，和煤层气厚度（CBMT）确定的“正交截距”的方法。形态测定分析显示，在取样组织中，高度可变的转基因相关BMT增加，肾小球BM显示出迄今为止最大的增加（+87%）。在视网膜、肺泡和胸腹膈中也观察到显著的厚度增加。BMT增加并不普遍;然而，大多数都适度扩大，对照组中最厚的那些通常显示出最大的增加。虽然糖尿病相关的CBM增加的发病机制知之甚少，但当前研究的数据显示，在OVE 26转基因小鼠中，BMT增加是高血糖症的常见伴随物。因此，高血糖诱导的微血管损伤可能是糖尿病BM疾病的一个促成因素，并且微血管细胞和细胞外异质性可能限制不同组织中CBM增厚的程度。(C)2003 Wiley-Liss，Inc.
Capillary basement membrane (CBM) thickening is an ultrastructural hallmark in diabetic patients and in animal models of diabetes. However, the wide variety of tissues sampled and diverse methods employed have made the interpretation of thickness data difficult. We showed previously that acellular glomerular BMs in OVE26 transgenic diabetic mice were thickened beyond normal age-related thickening, and in the current study we hypothesized that other microvascular BMs likewise would show increased widths relative to age-matched controls. Accordingly, a series of tissues, including skeletal and cardiac muscle, ocular retina and choriod, peripheral nerve, lung, pancreas, and renal glomerulus was collected from 300-350-day-old normal and transgenic mice. Transmission electron micrographs of cross sections through capillary walls were prepared, and CBM thickness (CBMT) was determined by the "orthogonal intercept" method. Morphometric analyses showed highly variable transgene-related BMT increases in the sampled tissues, with glomerular BM showing by far the greatest increase (+87%). Significant thickness increases were also seen in the retina, pulmonary alveolus, and thoracoabdominal diaphragm. BMT increases were not universal; however, most were modestly widened, and those that were thickest in controls generally showed the greatest increase. Although the pathogenesis of diabetes-related increases in CBM is poorly understood, data in the current study showed that in OVE26 transgenic mice increased BMT was a frequent concomitant of hyperglycemia. Accordingly, it seems likely that hyperglycemia-induced microvascular damage may be a contributing factor in diabetic BM disease, and that microvessel cellular and extracellular heterogeneity may limit the extent of CBM thickening in diverse tissues. (C) 2003 Wiley-Liss, Inc.