有氧运动调控磷酸钙纳米材料细胞毒性的抑制作用及机制

doi:10.11896/cldb.25040077

材料导报

2025, Vol. 39

Issue (15): 25040077-7 https://doi.org/10.11896/cldb.25040077

无机非金属及其复合材料

有氧运动调控磷酸钙纳米材料细胞毒性的抑制作用及机制

周慧晴¹, 王艺达¹, 陈欣¹, 郭庆¹, 曹世琦¹, 刘于谦¹, 肖瑞琳^2,*, 梁海霞^1,*

1 太原理工大学人工智能学院,山西晋中 030600
2 太原理工大学体育与健康工程学院,山西晋中 030600

The Inhibitory Effect and Mechanism of Aerobic Exercise on the Cytotoxicity of Calcium Phosphate Nanomaterials

ZHOU Huiqing¹, WANG Yida¹, CHEN Xin¹, GUO Qing¹, CAO Shiqi¹, LIU Yuqian¹, XIAO Ruilin^2,*, LIANG Haixia^1,*

1 College of Artifical Intelligence, Taiyuan University of Technology, Jinzhong 030600, Shanxi, China
2 College of Physical Education and Health Engineering, Taiyuan University of Technology, Jinzhong 030600, Shanxi, China

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摘要磷酸钙纳米材料(CaP)凭借其卓越的骨诱导性与可控降解性,在骨缺损修复与靶向治疗领域极具应用前景,但其引发的溶酶体膜透化(lysosomal membrane permeabilization,LMP)导致的细胞毒性仍是临床转化的核心障碍。本工作发现:(1)CaP在溶酶体酸性环境中迅速降解,释放大量Ca²⁺,导致溶酶体pH值升高和LMP增加,进而破坏溶酶体膜的稳定性;(2)有氧运动模拟剂AICAR可诱导VMA21的表达水平显著升高,促进V-ATPase的V₀/V₁亚基组装,增强溶酶体膜的稳定性,抑制LMP的发生,显著减轻CaP诱导的细胞毒性;(3)在动物水平上,有氧运动通过减轻CaP诱导的多器官组织病理损伤,并恢复血清中肝肾功能损伤指标至正常水平。上述研究结果为CaP的生物安全性优化提供了“内源性防御”新策略,推动了纳米医学从“被动毒性抑制”向“运动调节干预”的范式革新。

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	周慧晴
	王艺达
	陈欣
	郭庆
	曹世琦
	刘于谦
	肖瑞琳
	梁海霞

关键词: 磷酸钙有氧运动溶酶体膜稳定性溶酶体膜通透化

Abstract: Calcium phosphate nanoparticles (CaP) exhibit substantial promise in bone defect repair and targeted therapy owing to their exceptional osteoinductivity and controllable degradability. However, the cytotoxicity due to lysosomal membrane permeabilization (LMP) triggered by these nanoparticles remains a key obstacle to their clinical translation. This study illustrates the protective effects of aerobic exercise against CaP-induced lysosomal dysfunction. We show that CaP undergoes rapid degradation in the acidic lysosomal milieu, which leads to the release of abundant Ca²⁺ ions that elevate lysosomal pH and enhance LMP, thereby destabilizing the lysosomal membrane. The aerobic exercise mimetic AICAR effectively mitigates this toxicity by upregulating VMA21 expression, promoting the assembly of V₀/V₁ subunits of V-ATPase (vacuolar-type ATPase), and reinforcing lysosomal membrane stability to suppress LMP. Mechanistically, AICAR activates the AMPK signaling pathway to restore the lysosomal proton gradient and counteract Ca²⁺-induced osmotic imbalance, thereby preserving lysosomal integrity. At the animal le-vel, aerobic exercise alleviates CaP-induced histopathological damage in multiple organs and restores serum markers of liver and kidney injury to normal levels. These findings provide a novel "endogenous defense" strategy for optimizing the biosafety of calcium phosphate nanoparticles (CaP), driving a paradigm shift in nanomedicine from "passive toxicity inhibition" to "exercise-modulated intervention".

Key words: calcium phosphate aerobic exercise lysosomal membrane stability lysosomal membrane permeabilization

出版日期: 2025-08-10 发布日期: 2025-08-13

ZTFLH:

Q375

基金资助: 国家自然科学基金(31501124)

通讯作者: 肖瑞琳,太原理工大学体育与健康工程学院讲师。目前主要从事运动诱导的亚细胞结构适应性变化的分子机制研究。xiaoruilin@tyut.edu.cn
梁海霞,太原理工大学人工智能学院副教授、硕士研究生导师。目前主要从事微生物制复合材料的设计合成,利用以“基因调控·工程设计”为核心的合成生物学技术,构建环境友好的增强材料表面改性方法。通过基因编辑等技术人工调控微生物代谢途径,利用特定代谢产物,对增强材料进行表面修饰,制备形成有序排列、结构优异的天然有机-无机复合材料,实现改善复合材料界面结合的目的。lianghaixia@tyut.edu.cn

作者简介: 周慧晴,现为太原理工大学人工智能学院硕士研究生,在梁海霞副教授的指导下进行研究。目前主要研究领域为微生物纳米材料。

引用本文:

周慧晴, 王艺达, 陈欣, 郭庆, 曹世琦, 刘于谦, 肖瑞琳, 梁海霞. 有氧运动调控磷酸钙纳米材料细胞毒性的抑制作用及机制[J]. 材料导报, 2025, 39(15): 25040077-7.
ZHOU Huiqing, WANG Yida, CHEN Xin, GUO Qing, CAO Shiqi, LIU Yuqian, XIAO Ruilin, LIANG Haixia. The Inhibitory Effect and Mechanism of Aerobic Exercise on the Cytotoxicity of Calcium Phosphate Nanomaterials. Materials Reports, 2025, 39(15): 25040077-7.

链接本文:

https://www.mater-rep.com/CN/10.11896/cldb.25040077 或 https://www.mater-rep.com/CN/Y2025/V39/I15/25040077

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