Department of Vascular Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Vascular Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Eur J Vasc Endovasc Surg. 2024 Apr;67(4):663-671. doi: 10.1016/j.ejvs.2023.10.018. Epub 2023 Oct 19.
Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development.
C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for four weeks plus β-aminopropionitrile (BAPN, 1 mg/mL) for the first two weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promoted aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for two weeks.
The maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in the aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of the non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. The maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice.
Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.
硒（Se）是机体氧化防御系统的关键组成部分。然而，硒是否影响主动脉瘤（AA）的发展尚不清楚。本动物实验旨在阐明 Se 在 AA 发展中的作用。
C57BL/6N 雄性小鼠连续 8 周分别饲以 Se 缺乏（Se-D，<0.05mg/kg）、Se 充足（Se-A，0.2mg/kg）或 Se 补充（Se-S，1mg/kg）饲料。随后，用血管紧张素Ⅱ（Ang II，1mg/kg/min）持续 4 周，前 2 周加用β-氨基丙腈（BAPN，1mg/mL）建立 AA 小鼠模型（Se-D，n=11；Se-A，n=12；Se-S，n=15）。在建模过程中，用生理盐水替代 Ang II，BAPN 被移除，Sham 组（Se-A，n=9）小鼠用相同方法处理。为了确定 Se 缺乏是否通过基质金属蛋白酶-2（MMP-2）促进主动脉扩张，将非特异性 MMP 抑制剂强力霉素（Dox，100mg/kg/day）给予 Se-D AA 小鼠（n=7），持续 2 周。
与 Se-A AA 模型组相比，Se-D AA 模型组小鼠的最大主动脉直径显著增加。与 Se-A AA 模型组相比，Se-D AA 模型组小鼠主动脉中层的 MMP-2 表达和活性显著增加。在 Se-D AA 模型组非扩张主动脉中层发现大量血管平滑肌细胞（VSMCs）聚集，强力霉素完全抑制了这种聚集。与 Se-A AA 模型组相比，Se-D AA 模型组小鼠主动脉中层的 VSMCs 比例显著升高。与 Se-D AA 模型组相比，用强力霉素处理的 Se-D AA 模型组小鼠的最大主动脉直径和 AA 发生率明显降低。
Se 缺乏通过增加血管平滑肌细胞衍生的 MMP-2 的表达和活性促进 AA 模型小鼠的主动脉扩张，导致主动脉中层 VSMCs 异常聚集和增殖。
