Department of Cardiology, The Second Affliated and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 312500, China; Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Department of Cardiology, The Second Affliated and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 312500, China.
Phytomedicine. 2022 Sep;104:154336. doi: 10.1016/j.phymed.2022.154336. Epub 2022 Jul 11.
The pathogenesis of myocardial ischemia/reperfusion is complex, involving multiple regulatory genes and environmental factors, and requiring the simultaneous regulation of multiple targets. Meanwhile, Traditional Chinese Medicine (TCM) has certain advantages in the comprehensive treatment of multi-site, multi-target conditions and overall regulation of this condition. This study explores the effect of the well-known TCM, the Shexiang Baoxin Pill (SBP) on myocardial ischemia/reperfusion injury in mice.
In vivo, 20 mg/kg/day SBP was administered by gavage for 28 days. In vitro, cardiomyocytes were pretreated with 25 μg/ml SBP for 24 h. Evans blue/TTC double-staining was employed to determine the infarct size. Markers of myocardial injury were detected in the serum and cell supernatants. The changes of pyroptosis and autophagy proteins were detected by western blot. Immunofluorescence, immunohistochemistry and PCR were performed to further illustrate the results.
SBP significantly reduced the myocardial infarct size, decreased the myocardial injury markers, inhibited cardiomyocyte pyroptosis and oxidative stress, and promoted autophagy in vivo. In vitro, SBP alleviated cardiomyocyte pyroptosis, inhibited oxidative stress, reduced IL-1β and IL-18 secretion, and unblocked autophagy flux. Myocardial injury is mitigated by SBP via the rapid degradation of autophagosomes, and SBP promotes the accumulation of autophagosomes by downregulating mmu_circ_0005874, Map3k8 and upregulating mmu-miR-543-3p.
We found for the first time that SBP can inhibit pyroptosis and oxidative stress, and protect from myocardial I/R injury. In addition, it inhibits pyroptosis and improves H/R injury by promoting autophagosome generation and accelerating autophagic flux. SBP interferes with autophagy through the interaction between mmu_circ_0005874/mmu-miR-543-3p/Map3k8.
心肌缺血/再灌注的发病机制复杂，涉及多个调节基因和环境因素，需要同时调节多个靶点。同时，中药在多部位、多靶点的综合治疗和整体调节方面具有一定优势。本研究探讨了著名中药麝香保心丸（SBP）对小鼠心肌缺血/再灌注损伤的作用。
体内实验中，给予小鼠每天灌胃 20mg/kg SBP，共 28 天；体外实验中，用 25μg/ml SBP 预处理心肌细胞 24h。采用伊文思蓝/TTC 双重染色法测定梗死面积。检测血清和细胞上清液中心肌损伤标志物。用 Western blot 检测细胞焦亡和自噬相关蛋白的变化。免疫荧光、免疫组化和 PCR 进一步阐明结果。
SBP 显著减小心肌梗死面积，降低心肌损伤标志物，抑制心肌细胞焦亡和氧化应激，促进体内自噬。体外实验中，SBP 减轻心肌细胞焦亡，抑制氧化应激，减少 IL-1β和 IL-18 的分泌，并解除自噬流阻断。SBP 通过快速降解自噬体减轻心肌损伤，通过下调 mmu_circ_0005874、Map3k8 和上调 mmu-miR-543-3p 促进自噬体的积累。
我们首次发现 SBP 可抑制心肌 I/R 损伤中的焦亡和氧化应激。此外，它还通过促进自噬体生成和加速自噬流来抑制细胞焦亡并改善 H/R 损伤。SBP 通过 mmu_circ_0005874/mmu-miR-543-3p/Map3k8 相互作用干扰自噬。
