MicroCT analysis of vascular morphometry: a comparison of right lung lobes in the SUGEN/hypoxic rat model of pulmonary arterial hypertension.
MicroCT analysis of vascular morphometry: a comparison of right lung lobes in the SUGEN/hypoxic rat model of pulmonary arterial hypertension.
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DOI：
10.1177/2045893217709001
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发表时间：
2017-04
影响因子：
2.6
通讯作者：
Shields KJ
中科院分区：
文献类型：
--
作者：
Faight EM;Verdelis K;Zourelias L;Chong R;Benza RL;Shields KJ
肺动脉高压（PAH）是一种罕见的疾病，其特征是肺内显著的血管重塑。临床计算机断层扫描（CT）通常用于辅助PAH诊断。PAH的动物模型，包括Sugen-缺氧大鼠模型（SU/hyp），密切模拟人类PAH的发展。我们以前使用微型计算机断层扫描（microCT）发现广泛的右肺血管重塑SU/hypp。我们假设单个右肺叶对整个肺血管重塑的贡献可能不相等。对Sprague-Dawley大鼠皮下注射血管内皮生长因子受体阻断剂（Sugen 5416），随后暴露于慢性缺氧条件（10%O2）3周。用不透明树脂（Microfil）灌注肺血管后，以10 µm体素分辨率对右肺叶进行显微CT成像，并对每个肺叶分别进行3D形态测定分析。正如预期的那样，我们发现SU/hypp组的血管体积与总叶体积的比值显著低于对照组，但仅限于远叶（下方：0.23 [0.21-0.30] vs 0.35 [0.27-0.43]，P = 0.02;附件：0.27 [0.25-0.33] vs 0.37 [0.29-0.43]，P = 0.06）。总的来说，我们观察到两组远侧叶的连续血管明显减少，血管密度降低，而血管腔直径更大（P < 0.05）。此外，SU/hypp叶内的血管分离和血管表面积与体积比在SU/hypp叶中显著大于对照组（P < 0.03）。检查参数的结果支持SU/hypp模型中的整体广泛血管重塑，并表明这可能是肺叶依赖性的。
Pulmonary arterial hypertension (PAH) is a rare disease characterized by significant vascular remodeling within the lung. Clinical computed tomography (CT) scans are routinely used to aid in PAH diagnosis. Animal models, including the Sugen-hypoxic rat model (SU/hyp), of PAH closely mimic human PAH development. We have previously used micro-computed tomography (microCT) to find extensive right lung vascular remodeling in the SU/hyp. We hypothesized that the individual right lung lobes may not contribute equally to overall lung vascular remodeling. Sprague-Dawley rats were subjected to a subcutaneous injection of vascular endothelial growth factor receptor blocker (Sugen 5416) and subsequently exposed to chronic hypoxic conditions (10% O2) for three weeks. Following perfusion of the lung vasculature with an opaque resin (Microfil), the right lung lobes were microCT-imaged with a 10-µm voxel resolution and 3D morphometry analysis was performed separately on each lobe. As expected, we found a significantly lower ratio of vascular volume to total lobe volume in the SU/hyp compared with the control, but only in the distal lobes (inferior: 0.23 [0.21–0.30] versus 0.35 [0.27–0.43], P = 0.02; accessory: 0.27 [0.25–0.33] versus 0.37 [0.29–0.43], P = 0.06). Overall, we observed significantly fewer continuous blood vessels and reduced vascular density while having greater vascular lumen diameters in the distal lobes of both groups (P < 0.05). In addition, the vascular separation within the SU/hyp lobes and the vascular surface area to volume ratio were significantly greater in the SU/hyp lobes compared with controls (P < 0.03). Results for the examined parameters support the overall extensive vascular remodeling in the SU/hyp model and suggest this may be lobe-dependent.