Pellenc Quentin, El Bitar Sandy, Darmon Arthur, Dupont Sébastien, Michel Jean-Baptiste, Jondeau Guillaume
Vascular and Thoracic Surgery Department, Bichat Hospital, Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France.
Centre de Référence pour le Syndrome de Marfan et apparentés, Bichat Hospital, Assistance Publique-Hopitaux de Paris (AP-HP), Paris, France.
J Vasc Res. 2022;59(6):369-380. doi: 10.1159/000526417. Epub 2022 Nov 10.
Beta-aminopropionitrile (BAPN) administration is a chemically induced model for preclinical aortic pathologies research. Angiotensin II (AngII) has been widely used to promotes aortic dissections in mice. Here, we provide insight on a modified aortic dissection model in rats. The effect of smooth muscle cell (SMC) relaxation with vasodilators is studied in this model.
Forty Sprague-Dawley rats were divided in 4 groups: control, isosorbide dinitrate (ISDN, 30 mg/kg/day) in the drinking water, BAPN (0.02%) in the food, BAPN + ISDN (same doses). Thoracic and abdominal aortic diameters were evaluated through transthoracic ultrasound echography. After 6 weeks, all rats were infused with AngII (1 mg/kg/day) subcutaneously. Survival and type of aortic events were numbered. Histological and histochemical analyses of aorta were performed.
Initial telesystolic ascending aorta diameters were equal in all groups and became significantly larger in the BAPN + ISDN group compared to the BAPN group (control: 3.37 ± 0.17 mm, ISDN: 3.49 ± 0.16 mm, BAPN: 3.53 ± 0.13 mm, BAPN + ISDN: 3.61 ± 0.16 mm, analysis of variance p < 0.0001). BAPN followed by AngII infusion showed a significant lower survival rate (p = 0.029) and produced a large panel of aortic events. Association of ISDN and BAPN significantly reduces survival (p = 0.001) and provides more aortic events compared to BAPN alone (p = 0.031). In both BAPN-treated groups, orcein staining revealed split and dissected elastic fibers in the media, alcian blue staining showed mucoid degeneration of the aortic wall, and Perls-diaminobenzidine staining revealed an accumulation of Fe2+.
SMC relaxation with ISDN increases aortic dilatation, worsens aortic prognosis, and reproduces human histological findings in a low-dose BAPN/AngII-induced aortic dissection model in rats.
给予β-氨基丙腈（BAPN）是一种用于临床前主动脉病变研究的化学诱导模型。血管紧张素II（AngII）已被广泛用于促进小鼠主动脉夹层形成。在此，我们介绍一种改良的大鼠主动脉夹层模型。在该模型中研究了血管舒张剂对平滑肌细胞（SMC）舒张的影响。
将40只Sprague-Dawley大鼠分为4组：对照组、饮用水中含硝酸异山梨酯（ISDN，30mg/kg/天）组、食物中含BAPN（0.02%）组、BAPN + ISDN（相同剂量）组。通过经胸超声心动图评估胸主动脉和腹主动脉直径。6周后，所有大鼠皮下注射AngII（1mg/kg/天）。记录生存情况和主动脉事件类型。对主动脉进行组织学和组织化学分析。
所有组的初始收缩末期升主动脉直径相等，与BAPN组相比，BAPN + ISDN组的直径显著增大（对照组：3.37±0.17mm，ISDN组：3.49±0.16mm，BAPN组：3.53±0.13mm, BAPN + ISDN组：3.61±0.16mm，方差分析p<0.0001）。先给予BAPN再输注AngII显示生存率显著降低（p = 0.029），并产生大量主动脉事件。与单独使用BAPN相比，ISDN与BAPN联合使用显著降低生存率（p = 0.001），并导致更多主动脉事件（p = 0.031）。在两个BAPN治疗组中，orcein染色显示中膜弹性纤维分裂和剥离，阿尔辛蓝染色显示主动脉壁黏液样变性，Perls-二氨基联苯胺染色显示Fe2+积累。
在低剂量BAPN/AngII诱导的大鼠主动脉夹层模型中，ISDN使SMC舒张会增加主动脉扩张，恶化主动脉预后，并重现人类组织学表现。
