Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China; Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, Henan, China.
Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China.
Microvasc Res. 2022 Jul;142:104370. doi: 10.1016/j.mvr.2022.104370. Epub 2022 Apr 21.
Balloon angioplasty, stent implantation, and application of an arterial clamp during surgery can induce artery injury such as elastin breaks and endothelium injury, but there is little research focused on the injury induced by these therapeutic manipulations. We established a simple and reproducible small animal aortic injury model and examined intramural injection as a potential therapeutic method to alleviate injury.
The abdominal aorta of male Sprague Dawley (SD) rats or C57BL/6 J mice was clamped sequentially throughout its length. Transforming growth factor β1 (TGFβ1), SB431542, lipopolysaccharide (LPS), Necrostatin-1 (Nec-1), rapamycin, or MHY1485 contained in Pluronic gel was injected intramurally at day 0 or day 7. Animals were fed with chow containing 0.25% beta-aminopropionitrile (BAPN) to evaluate the influence of BAPN. All samples were harvested and examined by immunohistochemistry and immunofluorescence.
The clamped rat aorta showed luminal dilation, elastin fiber breaks, neointimal hyperplasia, and dissection (days 0-90). Intramural injection of TGFβ1, rapamycin and Nec-1 showed a protective effect on the injured aorta, whereas SB431542, MHY1485 and LPS showed more severe wall damage. The aortic lumen in rats fed with BAPN was significantly larger than in control rats (day 7). Mouse aorta showed similar injury with neointimal hyperplasia and elastin fiber breaks.
The rodent arterial injury model is reproducible and may mimic early changes of arterial injury. The model accommodates intramural injection of different drugs that may show mechanisms of arterial injury. Although this is a preliminary animal model, the intramural injection method may have potential clinical application in the future.
球囊血管成形术、支架植入术和手术中应用动脉夹会引起动脉损伤，如弹力纤维断裂和内皮损伤，但目前针对这些治疗操作引起的损伤研究较少。我们建立了一种简单且可重复的小型动物主动脉损伤模型，并研究了腔内注射作为一种潜在的治疗方法来减轻损伤。
雄性 Sprague Dawley（SD）大鼠或 C57BL/6J 小鼠的腹主动脉被全长依次夹闭。在第 0 天或第 7 天，将转化生长因子β1（TGFβ1）、SB431542、脂多糖（LPS）、 Necrostatin-1（Nec-1）、雷帕霉素或 MHY1485 注入到 Pluronic 凝胶中进行腔内注射。动物喂食含 0.25%β-氨基丙腈（BAPN）的饲料，以评估 BAPN 的影响。所有样本均通过免疫组织化学和免疫荧光染色进行检测。
夹闭大鼠的主动脉出现管腔扩张、弹力纤维断裂、新生内膜增生和夹层（第 0-90 天）。腔内注射 TGFβ1、雷帕霉素和 Nec-1 对损伤的主动脉具有保护作用，而 SB431542、MHY1485 和 LPS 则显示出更严重的管壁损伤。喂食 BAPN 的大鼠的主动脉腔明显大于对照组（第 7 天）。小鼠的主动脉也出现了类似的损伤，包括新生内膜增生和弹力纤维断裂。
该啮齿动物动脉损伤模型具有可重复性，可能模拟动脉损伤的早期变化。该模型可容纳不同药物的腔内注射，这些药物可能具有动脉损伤的机制。尽管这是一个初步的动物模型，但腔内注射方法在未来可能具有潜在的临床应用。
