Yang Xiaochun, Wu Wei, Huang Weitian, Fang Junfeng, Chen Yunli, Chen Xiaoyan, Lin Xiaolan, He Yanbin
The First Clinical College of Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.
Department of Rehabilitation, Guangdong Work Injury Rehabilitation Hospital, Guangzhou, Guangdong 510000, P.R. China.
Mol Med Rep. 2025 May;31(5). doi: 10.3892/mmr.2025.13491. Epub 2025 Mar 14.
Atherosclerosis (AS) is a disease with high global incidence and mortality rates. Currently, the treatment of AS in clinical practice carries a high risk of adverse effects and toxic side effects. The pretreatment of mesenchymal stem cells (MSCs) with drugs may enhance the bioactivity of MSC‑derived exosomes (MSC‑exos), which could be a promising candidate for inhibiting the progression of AS. The aim of the present study was to investigate the ability of exos derived from baicalin‑preconditioned MSCs (Ba‑exos) to exhibit an inhibitory effect on AS progression and to explore the potential molecular mechanisms. Exos were isolated from untreated MSCs and MSCs pretreated with Ba, and were characterized using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Subsequently, Cell Counting Kit‑8 and Transwell assays, reverse transcription‑quantitative PCR, immunofluorescence, western blotting and ELISA were used to evaluate the effects of Ba‑exos on AS, and the possible molecular mechanisms. Oil Red O and Masson staining were used to assess AS pathological tissue in a high‑fat diet‑induced mouse model of AS. Notably, MSC‑exos and Ba‑exos were successfully isolated. Compared with MSC‑exos, Ba‑exos demonstrated superior inhibitory effects on the viability and migration, and the levels of inflammatory factors in oxidized low‑density lipoprotein (ox‑LDL)‑induced vascular smooth muscle cells (VSMCs). Additionally, compared with MSC‑exos, Ba‑exos significantly inhibited NF‑κB activation by upregulating sirtuin 1 (SIRT1), thereby suppressing inflammation in ox‑LDL‑induced VSMCs to a greater extent. In mice with high‑fat diet‑induced AS, Ba‑exos exhibited the ability to inhibit AS plaque formation and to alleviate AS progression by reducing the levels of inflammatory factors compared with MSC‑exos; however, the difference was not significant. In conclusion, Ba‑exos may serve as a potential strategy for treating AS by regulating the SIRT1/NF‑κB signaling pathway to suppress inflammation.
动脉粥样硬化（AS）是一种在全球发病率和死亡率都很高的疾病。目前，临床实践中AS的治疗存在很高的不良反应和毒副作用风险。用药物对间充质干细胞（MSCs）进行预处理可能会增强MSC来源的外泌体（MSC-exos）的生物活性，这可能是抑制AS进展的一个有前景的候选方法。本研究的目的是研究黄芩苷预处理的MSCs来源的外泌体（Ba-exos）对AS进展的抑制作用，并探索其潜在的分子机制。从未经处理的MSCs和用黄芩苷预处理的MSCs中分离出外泌体，并通过透射电子显微镜、纳米颗粒跟踪分析和蛋白质印迹进行表征。随后，使用细胞计数试剂盒-8和Transwell实验、逆转录-定量PCR、免疫荧光、蛋白质印迹和酶联免疫吸附测定来评估Ba-exos对AS的影响及其可能的分子机制。用油红O和Masson染色评估高脂饮食诱导的AS小鼠模型中的AS病理组织。值得注意的是，成功分离出了MSC-exos和Ba-exos。与MSC-exos相比，Ba-exos对氧化型低密度脂蛋白（ox-LDL）诱导的血管平滑肌细胞（VSMCs）的活力和迁移以及炎症因子水平具有更强的抑制作用。此外，与MSC-exos相比，Ba-exos通过上调沉默调节蛋白1（SIRT1）显著抑制核因子κB（NF-κB）的激活，从而在更大程度上抑制ox-LDL诱导的VSMCs中的炎症。在高脂饮食诱导的AS小鼠中，与MSC-exos相比，Ba-exos表现出抑制AS斑块形成和通过降低炎症因子水平来缓解AS进展的能力；然而，差异不显著。总之，Ba-exos可能是一种通过调节SIRT1/NF-κB信号通路抑制炎症来治疗AS的潜在策略。
