Liu Fei Xiang, Niu Yu Ge, Zhang Dao Pei, Zhang Huai Liang, Zhang Zhen Qiang, Sun Rui Qin, Zhang Yun Ke
The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Henan Vertigo Disease Diagnosis and Treatment Center, Zhengzhou, China.
Front Neurol. 2022 Apr 18;13:860541. doi: 10.3389/fneur.2022.860541. eCollection 2022.
This study aimed to construct an animal model of intracranial arterial dolichoectasia (IADE) applying the modified modeling protocol.
Twenty five milliunits elastase and inactivated elastase were, respectively, injected into the cerebellomedullary cistern of 60 C57/BL6 mice which were divided into experimental group (EG, = 30) and control group (CG, = 30) by using a computer-based random order generator. The modified modeling protocol clarified these aspects including brain three-dimensional parameters of mouse head fixation, angle of head inclination, fixed position of taper ear, needle holding technique, needle entry depth, prevention of liquid drug back flow, and storage conditions of elastase. And it was observed for the following parts such as mortality, inflammatory factors, craniocerebral arteries scanning, vascular tortuosity index, artery diameter, pathology of the cerebrovascular.
Within differently surveyed stage, the total mortality of mice in EG was 20%. ELISA illustrated that the levels of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor α (TNF-α) in peripheral blood were increased significantly after modeling. Angiography indicated that 100% of IADE in EG were observed and the diameter and tortuosity index of the basilar artery were significantly increased ( < 0.01). EVG histological processing and staining showed the disrupted internal elastic lamina, the atrophied muscle layer, and the hyalinized connective tissue of the basilar artery with the vascular wall tunica media in EG. Micro-computed tomography reported that the craniocerebral arteries of the mice in EG were outstandingly elongated, tortuous, and dilated.
The modified modeling protocol can reduce the mortality, improve the success rate, and provide a stable animal model for IADE.
本研究旨在应用改良建模方案构建颅内动脉扩张症（IADE）动物模型。
将25毫单位弹性蛋白酶和灭活弹性蛋白酶分别注入60只C57/BL6小鼠的小脑延髓池，通过计算机随机排序发生器将其分为实验组（EG，n = 30）和对照组（CG，n = 30）。改良建模方案明确了以下方面，包括小鼠头部固定的脑三维参数、头部倾斜角度、锥形耳固定位置、持针技术、进针深度、防止液体药物回流以及弹性蛋白酶储存条件。并对死亡率、炎症因子、颅脑动脉扫描、血管迂曲指数、动脉直径、脑血管病理学等部分进行观察。
在不同观察阶段，EG组小鼠总死亡率为20%。ELISA显示建模后外周血中基质金属蛋白酶-9（MMP-9）和肿瘤坏死因子α（TNF-α）水平显著升高。血管造影显示EG组IADE观察率为100%，基底动脉直径和迂曲指数显著增加（P < 0.01）。EG组基底动脉经弹力纤维染色（EVG）组织学处理及染色显示内弹性膜破坏、肌层萎缩、结缔组织玻璃样变，血管壁中膜受累。微计算机断层扫描报告显示EG组小鼠颅脑动脉明显伸长、迂曲和扩张。
改良建模方案可降低死亡率，提高成功率，为IADE提供稳定的动物模型。
