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通过纳米颗粒引导M2型巨噬细胞极化实现小鼠功能性肌肉恢复

更新时间:2026-08-20   点击次数:34次

中文摘要:

炎症的持续存在及其对组织再生的相关限制,被认为部分归因于M1型巨噬细胞相对于M2型巨噬细胞的失衡。在此,我们假设提供一种持续释放的抗炎性极化细胞因子,能够改变组织损伤部位巨噬细胞的平衡,从而改善功能性再生。具体而言,我们将IL-4偶联金纳米颗粒(PA4)注射至小鼠受损骨骼肌中,结果显示,与仅注射溶剂的对照组小鼠相比,PA4治疗组小鼠的组织学表现得到改善,肌肉力量提高了约40%。巨噬细胞是主要的浸润免疫细胞,与溶剂对照组相比,PA4治疗组中表达M2a表型的巨噬细胞比例增加了约两倍,而M1型巨噬细胞比例则减少了约两倍。肌肉注射可溶性IL-4未能在功能上改善肌肉,也未改变巨噬细胞的极化状态。荷兰Liposoma氯膦酸盐脂质体单核/巨噬细胞的耗竭消除了PA4的治疗效果,表明肌肉功能的改善源于向M2型巨噬细胞极化的转变。PA4在体内引导巨噬细胞极化的能力,可能对多种损伤和炎症性疾病的治疗具有潜在益处。




英文摘要:

Persistence of inflammation, and associated limits in tissue regeneration, are believed to be due in part to the imbalance of M1 over M2 macrophages. Here, we hypothesized that providing a sustained source of an antiinflammatory polarizing cytokine would shift the balance of macrophages at a site of tissue damage to improve functional regeneration. Specifically, IL-4–conjugated gold nanoparticles (PA4) were injected into injured murine skeletal muscle, resulting in improved histology and an ∼40% increase in muscle force compared with mice treated with vehicle only. Macrophages were the predominant infiltrating immune cell, and treatment with PA4 resulted in an approximately twofold increase in the percentage of macrophages expressing the M2a phenotype and an approximately twofold decrease in M1 macrophages, compared with mice treated with vehicle only. Intramuscular injection of soluble IL-4 did not shift macrophage polarization or result in functional muscle improvements. Depletion of monocytes/macrophages eliminated the therapeutic effects of PA4, suggesting that improvement in muscle function was the result of M2-shifted macrophage polarization. The ability of PA4 to direct macrophage polarization in vivo may be beneficial in the treatment of many injuries and inflammatory diseases.



论文信息:

论文题目:Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice

期刊名称:PNAS

时间期卷:115 (42) 10648-10653

在线时间:2018年10月1日

DOI: 10.1073/pnas.1806908115

产品信息:

货号:CP-010-010

规格:10ml+10ml

品牌:Liposoma

产地:荷兰

名称:Clodronate Liposomes&Control Liposomes

办事处:靶点科技


Clodronate Liposomes氯膦酸盐脂质体清除肌肉巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于PNAS:通过纳米颗粒引导M2型巨噬细胞极化实现小鼠功能性肌肉恢复。

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Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法:

In vivo macrophage depletion

Macrophage Depletion. Clodronate and PBS liposomes were purchased from Liposoma (SKU: LIP-01). Liposomes (70uL) were administered retro-orbitally 2 days before surgery, and again on days 1 and 5 after surgery (Fig. S1A); 10uL were also administered intramuscularly into the ischemic TA 1 day before surgery, and again on days 2 and 7 after surgery.



巨噬细胞清除材料和方法文献截图:

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