中性粒细胞膜包覆的PLGA纳米粒促进小鼠心肌缺血再灌注损伤后修复

陈婧; 宋亚楠; 黄浙勇; 葛均波

doi:10.12025/j.issn.1008-6358.2025.20250194

中性粒细胞膜包覆的PLGA纳米粒促进小鼠心肌缺血再灌注损伤后修复

Neutrophil membrane-coated PLGA nanoparticles promoting the repair of myocardial ischemia-reperfusion injury in mice

摘要

摘要:
目的探讨中性粒细胞膜包覆的聚乳酸-羟基乙酸共聚物poly(lactic-co-glycolic acid)，PLGA纳米粒（Neu-NP）在小鼠急性心肌缺血再灌注（myocardial ischemia-reperfusion，MI/R）损伤后心脏修复中的作用及相关机制。
方法采用雄性C57小鼠构建急性MI/R损伤模型，随机分为PBS对照组（注射200 μL PBS）、NP治疗组（注射0.5 mg/mL NP 200 μL）和Neu-NP治疗组（注射0.5 mg/mL Neu-NP 200 μL）。提取中性粒细胞膜，与PLGA纳米粒融合制备Neu-NP。采用离体成像技术在MI/R损伤模型中评估Neu-NP的体内归巢能力，利用酶联免疫吸附试验检测给药1 d和3 d后小鼠心肌中肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）和白细胞介素6（interleukin-6，IL-6）的表达情况。采用超声心动图测定给药28 d后MI/R损伤小鼠心功能相关指标。免疫荧光染色观察小鼠心脏组织血管新生以及炎症细胞浸润情况。
结果将中性粒细胞膜与纳米颗粒进行仿生融合，成功构建了完整保留中性粒细胞表面关键炎症因子（TNF-α、IL-6）受体的Neu-NP。与PBS对照组及NP治疗组相比，给药1 d和3 d后Neu-NP治疗组小鼠受损心肌中TNF-α和IL-6表达水平明显下降（P＜0.05）；给药28 d后，Neu-NP治疗组小鼠心脏射血分数显著高于其余2组（P＜0.05）。免疫荧光染色提示心肌梗死区血管新生比例明显升高，炎症细胞浸润显著减少（P＜0.05）。
结论 Neu-NP在MI/R损伤后通过降低损伤区炎症因子水平，促进血管新生，在心肌梗死后心脏组织修复中发挥重要作用。

Abstract:
Objective To explore the role and related mechanism of neutrophil membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Neu-NP) in cardiac repair after acute myocardial ischemia-reperfusion (MI/R) injury in mice.
Methods The male C57 mouse model of acute MI/R injury was established and randomly divided into three groups: PBS control group (injection of 200 μL PBS), NP treatment group (injection of 0.5 mg/mL NP 200 μL), and Neu-NP treatment group (injection of 0.5 mg/mL Neu-NP 200 μL). Neutrophil membranes were extracted and fused with PLGA nanoparticles to construct biomimetic Neu-NP. The in vivo homing ability of Neu-NP was assessed using ex vivo imaging technology in the MI/R injury model, and the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the myocardium were measured using enzyme linked immunosorbent assay one day and three days after administration. Echocardiography was used to determine cardiac function indicators of MI/R injured mice 28 days post-administration. Immunofluorescence staining was used to observe angiogenesis repair and inflammatory cell infiltration in mouse heart tissue.
Results Neu-NP, engineered by integrating neutrophil membranes with nanoparticles, inherited surface receptors (TNF-αR and IL-6R) and functioned as decoys for inflammatory targeting. Compared with the PBS control group and NP treatment group, the secretion levels of TNF-α and IL-6 in the damaged myocardium of the Neu-NP treatment group were significantly decreased one and three days after administration (P＜0.05); 28 days after administration, the cardiac ejection fraction in the Neu-NP treatment group was significantly higher than that in the other two groups (P＜0.05). Immunofluorescence staining indicated a significant increase in the proportion of angiogenesis in the myocardial infarction area and a significant reduction in inflammation cell infiltration (P＜0.05).
Conclusions Neu-NP plays an important role in cardiac tissue repair after MI/R injury by alleviating inflammatory factors in the damaged area and promoting angiogenesis.

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