Department of Radiology, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Charitéplatz 1, Berlin 10117, Germany.
Department of Veterinary Medicine, Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, Building 12, Berlin 14163, Germany.
Contrast Media Mol Imaging. 2021 Apr 27;2021:9999847. doi: 10.1155/2021/9999847. eCollection 2021.
Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE-/- model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment.
Nine ApoE-/- mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE-/- animals without doxycycline treatment. Differences in mortality were also investigated between these groups.
In a previous study, we found that approximately 25% of angiotensin II-infused ApoE-/- mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE-/- mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE-/- mice showed significantly lower contrast-to-noise (CNR) values (=0.017) in MRI compared to ApoE-/- mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining ( = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment.
The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.
目前，腹主动脉瘤（AAA）尚无可靠的非手术治疗方法。因此，本研究旨在探讨强力霉素是否可减少载脂蛋白 E 基因敲除（ApoE-/-）小鼠 AAA 模型中的 AAA 生长和与破裂相关的死亡人数，以及基于钆塞酸二钠的 MRI 是否存在差异动物有无强力霉素治疗。
将 9 只 ApoE-/- 小鼠植入持续释放血管紧张素 II 的渗透微型泵，并同时给予强力霉素（30mg/kg/d）治疗。四周后，在 3T 上进行 MRI 检查，使用临床剂量的白蛋白结合探针钆塞酸二钠（0.03mmol/kg）。将结果与以前发表的野生型对照动物和以前研究过的无强力霉素治疗的 ApoE-/-动物进行比较。还研究了这些组之间死亡率的差异。
在之前的研究中，我们发现约 25%的血管紧张素 II 输注 ApoE-/- 小鼠死亡，而在本研究中，9 只血管紧张素 II 输注和强力霉素治疗的 ApoE-/- 小鼠中只有 1 只（11.1%）在 4 周内死亡。此外，与未接受强力霉素治疗的 ApoE-/- 小鼠相比，接受强力霉素治疗的 ApoE-/- 小鼠的 MRI 对比噪声（CNR）值显着降低（=0.017）。体内信号增强相对值（CNR）的测量与体外白蛋白染色的测量显着相关（r = 0.58）。此外，在荧光白蛋白染色中，白蛋白阳性区域与 LA-ICP-MS 中的镧分布之间表现出强烈的视觉共定位。然而，在强力霉素治疗后，未观察到动脉瘤大小的显着差异。
本实验性体内研究表明，强力霉素治疗可能通过减缓内皮损伤而不是逆转动脉瘤生长来减少 AAA 中的破裂相关死亡。
