背景:心肌损伤修复过程涉及复杂的细胞和分子机制,尤其是线粒体钙稳态、巨噬细胞的自噬与焦亡途径。中药在改善心肌损伤方面有显著的临床疗效,但其作用机制尚需深入研究。目的:探讨线粒体钙稳态介导的巨噬细胞自噬与焦亡途径在心肌损伤中的作用,并总结中药在这一领域的研究进展。方法:计算机检索Web of Science、PubMed及中国知网等数据库,从建库至2024年3月的相关文献。中文检索词为“线粒体钙稳态,巨噬细胞自噬,巨噬细胞焦亡,中药,心肌损伤,心肌损伤再灌注”等;英文检索词为“Mitochondrial calcium homeostasis,Macrophage autophagy,Macrophage pyroptosis,Traditional Chinese medicine,Myocardial injury”等。通过文献回顾分析线粒体钙稳态与巨噬细胞自噬、焦亡之间的关系,探究其在心肌损伤中的作用机制,总结中药多靶点、多通路影响的途径。结果与结论:①研究发现,线粒体钙稳态的维持与心肌细胞功能的正常运转密切相关。巨噬细胞可通过自噬与焦亡途径参与心肌损伤的修复过程,自噬有助于细胞的清除和炎症反应的调节,而焦亡则可通过释放炎症因子影响心肌修复。②中医药通过多种机制调节线粒体钙稳态和巨噬细胞功能,如黄芪甲苷通过降低线粒体膜电位和抑制细胞色素C来调节钙稳态,淫羊藿苷通过减少β-淀粉样蛋白沉积来发挥作用;中药复方和单味药物通过激活或抑制特定的信号通路,如PI3K/AKT、核因子κB等通路来促进心肌损伤的修复。③未来的研究应关注线粒体钙稳态、自噬与焦亡途径的相互作用,以及中药如何通过这些途径发挥治疗作用,为心肌损伤的治疗提供新的策略和药物。
Calcium is a crucial macronutrient and functions as a widespread signal in eukaryotes,ranging from yeast,plants to animals.As crucial second messengers,calcium ions(Ca^(2+))play indispensable roles in plant growth and development,response to external stressors,and signal transduction by modulating downstream cellular responses,including gene expression,metabolic activities,and transport functions[1,2].Unlike other nutrients,the levels of Ca^(2+)in the extracellular space and in certain intracellular stores are typically 10,000 times higher than resting cytoplasmic Ca^(2+)([Ca^(2+)]_(cyt))levels.This substantial gradient poses potential risks of[Ca^(2+)]_(cyt)overload and toxicity,and it can also lead to a rapid and transient increase in[Ca^(2+)]_(cyt),which is a key signaling mechanism for plants to respond to environmental cues.To mitigate the cytotoxicity of Ca^(2+)and continuously maintain the potential to generate specific Ca^(2+)signals,it is essential to keep the resting[Ca^(2+)]_(cyt)at a low level of approximately 100 nmol/L[3].Calcium homeostasis is fundamental for maintaining cellular function and organismal health in plants.
Songchong LuYan SunLichao MaSheng LuanGuofeng Yang
