解放军医学院学报2026,Vol.47Issue(3):236-246,11.DOI:10.12435/j.issn.2095-5227.25122402
脂质纳米颗粒封装的线粒体修复大鼠面神经损伤的实验研究
Repair of facial nerve injury with lipid nanoparticles-encapsulated mitochondria in rats
摘要
Abstract
Background Since early mitochondrial dysfunction constrains facial nerve regeneration,improving the therapeutic outcomes of mitochondrial transplantation through optimized delivery methods has become a primary research focus.Objective To construct lipid nanoparticles(LNP)-encapsulated engineered mitochondria(Mito@LNP)and evaluate their reparative effects in a rat buccal branch facial nerve crush injury model.Methods LNP was prepared by thin film hydration-extrusion method.Mitochondria were isolated from human umbilical cord mesenchymal stem cells(hUCMSC)and formulated into Mito@LNP.In vitro,PC12 cells were used to assess cytotoxicity,cellular uptake,and protection against H₂O₂-induced oxidative damage.In vivo,a rat buccal branch facial nerve crush model was established,and Mito@LNP was administered locally via subepineurial injection at the injury site.Small animal in vivo optical imaging system was employed to track mitochondrial distribution.Whisker movement analysis,electrophysiological testing,and immunofluorescence staining were performed to evaluate its neural repair effects.Results Mito@LNP was successfully fabricated,achieving a mitochondrial encapsulation efficiency of 89.4%.Compared with free mitochondria,LNP encapsulation enhanced mitochondrial uptake by PC12 cells(P<0.05).Under oxidative stress,Mito@LNP more effectively maintained ATP production(P<0.001)and mitochondrial membrane potential(P<0.05)in PC12 cells,thereby markedly improving cell viability(P<0.05).In vivo tracking indicated stronger retention and accumulation of Mito@LNP at the injured nerve(P<0.05).Rats treated with Mito@LNP showed substantially better recovery of whisker function(P<0.001)and compound muscle action potential(CMAP)parameters(P<0.05)than those receiving free mitochondria.Immunofluorescence staining further demonstrated that Mito@LNP significantly upregulated NF200(P<0.001)and S100β(P<0.05)expression in injured nerve tissue.Conclusion Mito@LNP markedly enhances repair and functional recovery after facial nerve crush injury in rats by improving mitochondrial delivery efficiency,and exhibits superior efficacy compared with free mitochondria.关键词
面神经/线粒体/脂质纳米颗粒/神经再生/大鼠Key words
facial nerve/mitochondrial/lipid nanoparticles/nerve regeneration/rats分类
医药卫生引用本文复制引用
王哲,程浩峰,崔钰惠,罗帅,苏天崎,王玉,张军..脂质纳米颗粒封装的线粒体修复大鼠面神经损伤的实验研究[J].解放军医学院学报,2026,47(3):236-246,11.基金项目
北京市自然科学基金项目(L254019) (L254019)