Liu Guochun, Zhao Binyi, Chen Qinglong, Li Xiang, Zhu Xuejiao, Duan Maowei, Zhang Mengdie, Liu Zhuohan, Wen Xuan, Guo Jia, Zheng Man, Wang Ruiyu, Luo Minghao
Chongqing Medical University, Chongqing, China.
The College of Exercise Medicine, Chongqing Medical University, Chongqing, China.
Sci Rep. 2025 Aug 19;15(1):30411. doi: 10.1038/s41598-025-05206-7.
Atherosclerosis (AS), driven by vascular endothelial dysfunction and poses a global health threat. This study compared the therapeutic effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on vascular endothelial function in early-stage AS mice, specifically investigating PCSK9 modulation and the TRX/TXNIP/NLRP3/GSDMD-N pathway. ApoE mice (n = 6/group) fed a high-fat diet for 12 weeks were randomized into sedentary (AS-S), HIIT (AS-HIIT), and MICT (AS-MICT) groups, with wild-type mice as control. Training lasted 12 weeks. Outcomes included body weight, lipid profiles (TG, TC, LDL-C, HDL-C), oxidative stress markers (T-SOD, GSH-Px, MDA), vascular function (eNOS expression, ACh-induced vasorelaxation), and TRX/TXNIP/NLRP3/GSDMD-N pathway activity. Both HIIT and MICT reduced body weight (p < 0.05) and improved lipid profile. Exercise groups showed reduced oxidative stress and inflammation pathways (p < 0.05). HIIT and MICT ameliorate early AS by reducing PCSK9 and oxidative/inflammatory pathway levels (p < 0.05), but HIIT demonstrates superior efficacy in improving endothelial function and pathway activation. These findings show HIIT and MICT mitigate endothelial dysfunction in early atherosclerotic mice via PCSK9 inhibition and advocate for HIIT as a prioritized strategy in early AS management.
动脉粥样硬化（AS）由血管内皮功能障碍引发，对全球健康构成威胁。本研究比较了高强度间歇训练（HIIT）和中等强度持续训练（MICT）对早期AS小鼠血管内皮功能的治疗效果，具体研究了前蛋白转化酶枯草溶菌素9（PCSK9）的调节作用以及硫氧还蛋白/硫氧还蛋白相互作用蛋白/NLR家族含pyrin结构域蛋白3/ Gasdermin D-N末端（TRX/TXNIP/NLRP3/GSDMD-N）通路。将喂食高脂饮食12周的载脂蛋白E小鼠（每组n = 6）随机分为久坐组（AS-S）、HIIT组（AS-HIIT）和MICT组（AS-MICT），以野生型小鼠作为对照。训练持续12周。观察指标包括体重、血脂谱（甘油三酯、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇）、氧化应激标志物（总超氧化物歧化酶、谷胱甘肽过氧化物酶、丙二醛）、血管功能（内皮型一氧化氮合酶表达、乙酰胆碱诱导的血管舒张）以及TRX/TXNIP/NLRP3/GSDMD-N通路活性。HIIT和MICT均降低了体重（p < 0.05）并改善了血脂谱。运动组的氧化应激和炎症通路水平降低（p < 0.05）。HIIT和MICT通过降低PCSK9以及氧化/炎症通路水平改善早期AS（p < 0.05），但HIIT在改善内皮功能和通路激活方面显示出更优的疗效。这些研究结果表明，HIIT和MICT通过抑制PCSK9减轻早期动脉粥样硬化小鼠的内皮功能障碍，并提倡将HIIT作为早期AS管理的优先策略。
