Regular transient limb ischemia (RTLI) can prevent atherosclerosis (AS) progression in hypercholesterolemic rabbits. This study aimed to investigate the minimum effective intensity and possible mechanisms of RTLI for preventing atherosclerosis. Eighty rabbits were divided into eight groups: normal (N), high cholesterol (H), three RTLI [three RTLI cycles every other day (R3qod), three RTLI cycles daily (R3qd), and six RTLI cycles daily (R6qd), each cycle of RTLI included 5 min of limb ischemia followed by 5 min limb reperfusion], and three correlated sham RTLI [sham ischemia for 30 min once every other day (S3qod), sham ischemia for 30 min once daily (S3qd), and sham ischemia for 60 min once daily (S6qd)]. Rabbits in group N were kept normally, while the others were fed 1% cholesterol diet for 12 weeks. The RTLI and sham RTLI groups were received RTLI or sham RTLI procedure, respectively. The plaque area in the thoracic aorta was determined by oil red O staining, and quantifying the ratio of plaque area to intimal area (PA/IA). Endothelium-dependent and -independent relaxation were also determined. Endothelial cell were isolated from abdominal aorta of rabbits, and the apoptosis ratio was detected using flow cytometry. The PA/IA and early apoptotic cell ratio was significantly lower as well as the endothelium-dependent relaxation response was higher in group R6qd than those in groups H and S6qd, while those in the R3qod group was not significantly different from those in groups H and S3qod, as well as those in the R3qd group showed no significant difference compared to those in groups H and S3qd. Six cycles of RTLI daily was the optimal effective intensity to prevent AS progression in rabbits. Endothelial function improvement and apoptosis inhibition might contribute to the anti-AS effects.

中文翻译：

---

规律性短暂性肢体缺血改善兔内皮功能并抑制内皮细胞凋亡预防动脉粥样硬化

定期短暂性肢体缺血（RTLI）可以预防高胆固醇血症兔的动脉粥样硬化（AS）进展。本研究旨在探讨 RTLI 预防动脉粥样硬化的最低有效强度及其可能机制。将 80 只兔子分为八组：正常组 (N)、高胆固醇组 (H)、三个 RTLI [每隔一天三个 RTLI 周期 (R3qod)、每天三个 RTLI 周期 (R3qd) 和每天六个 RTLI 周期 (R6qd)，每组RTLI 周期包括 5 分钟肢体缺血，随后 5 分钟肢体再灌注]，以及三个相关的假 RTLI [假缺血 30 分钟每隔一天一次 (S3qod)、假缺血 30 分钟每天一次 (S3qd) 和假缺血每天一次，每次 60 分钟（S6qd）]。 N组正常饲养，其余饲喂1%胆固醇饲料12周。 RTLI组和假RTLI组分别接受RTLI或假RTLI程序。通过油红O染色确定胸主动脉中的斑块面积，并量化斑块面积与内膜面积的比率（PA/IA）。还测定了内皮依赖性和非依赖性松弛。分离兔腹主动脉内皮细胞，流式细胞仪检测凋亡率。 R6qd 组 PA/IA 和早期凋亡细胞比值显着低于 H 组和 S6qd 组，内皮依赖性舒张反应高于 H 组和 S6qd 组，而 R3qod 组与 H 组和 S6qd 组无显着差异。 S3qod以及R3qd组与H组和S3qd组相比没有显着差异。每天六个周期的 RTLI 是预防家兔 AS 进展的最佳有效强度。内皮功能的改善和细胞凋亡的抑制可能有助于抗 AS 作用。