School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China.
Department of Central Laboratory, Lianshui County People's Hospital, Kangda College of Nanjing Medical University, Huaian, 223400, China.
Cardiovasc Toxicol. 2022 Sep;22(9):842-857. doi: 10.1007/s12012-022-09760-8. Epub 2022 Jul 9.
Salvianolic acid B (SalB) has been extensively investigated in our laboratory for myocardial ischemia (MI) disease. This study mainly aimed to illustrate the relationship between SIRT1 and the therapeutic effect of SalB on MI in rats and hypoxia damage in H9c2 cells. Furthermore, whether the antagonism of NLRP3 by SalB in the injuries mentioned above is related to SIRT1-AMPK-PGC-1α pathway-mediated mitochondrial biogenesis was further investigated. In vivo, 24 h after MI surgery, we found that SalB effectively reduced ST-segment elevation, myocardial infarct size enlargement, cardiac injury markers, myocardial structural abnormalities, and myocardial apoptotic cells in MI injury rats. In vitro, after 4 h of hypoxia exposure, SalB alleviated cell injury, inhibited the production of ROS and IL-1β, and prevented the loss of mitochondrial membrane potential (MMP). Besides, SalB downregulated the critical components of the NLRP3 inflammasome and upregulated the SIRT1-AMPK-PGC-1α signaling pathway-related molecules in myocardial tissues and H9c2 cells. However, all the above protective effects of SalB on MI could be offset by EX527. Taken together, our findings indicated that SalB could attenuate MI injury by targeting NLRP3, which is at least partially dependent on the SIRT1/AMPK/PGC-1α signaling pathway.
丹酚酸 B（SalB）在我们实验室中被广泛研究用于治疗心肌缺血（MI）疾病。本研究主要旨在阐明 SIRT1 与 SalB 对 MI 大鼠和 H9c2 细胞缺氧损伤的治疗作用之间的关系。此外，还进一步研究了 SalB 在上述损伤中对 NLRP3 的拮抗作用是否与 SIRT1-AMPK-PGC-1α 通路介导的线粒体生物发生有关。在体内，MI 手术后 24 小时，我们发现 SalB 可有效降低 ST 段抬高、心肌梗死面积扩大、心肌损伤标志物、心肌结构异常和 MI 损伤大鼠的心肌凋亡细胞。在体外，缺氧暴露 4 小时后，SalB 减轻细胞损伤，抑制 ROS 和 IL-1β 的产生，并防止线粒体膜电位（MMP）丧失。此外，SalB 下调心肌组织和 H9c2 细胞中 NLRP3 炎性小体的关键组成部分，并上调 SIRT1-AMPK-PGC-1α 信号通路相关分子。然而，SalB 对 MI 的所有上述保护作用均可被 EX527 抵消。总之，我们的研究结果表明，SalB 通过靶向 NLRP3 减轻 MI 损伤，这至少部分依赖于 SIRT1/AMPK/PGC-1α 信号通路。
