首页|氯膦酸盐脂质体通过消耗巨噬细胞延缓周围神经损伤后功能性修复的实验研究

氯膦酸盐脂质体通过消耗巨噬细胞延缓周围神经损伤后功能性修复的实验研究

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目的 探究巨噬细胞消耗对周围神经损伤修复的影响.方法 实验组小鼠腹腔注射氯膦酸盐脂质体消耗巨噬细胞后制备坐骨神经夹伤模型,另外部分小鼠注射空载脂质体后神经损伤作为对照组.术后7 d利用免疫荧光检测F4/80阳性巨噬细胞和GAP43阳性再生轴突.术后28d再次进行免疫荧光检测F4/80阳性巨噬细胞,并通过行为学、神经电生理检测运动功能和神经传导功能,腓肠肌称重和HE染色评估靶区肌萎缩.结果 术后7 d和28 d,实验组神经夹伤远端巨噬细胞消耗效率均达到70%以上,术后7 d神经远端的GAP43阳性再生轴突比对照组更少、更短.术后28 d,实验组小鼠的运动能力和神经传导强度显著下降,神经传导潜伏期延长,腓肠肌湿重比和肌纤维面积显著变小.结论 氯膦酸盐脂质体通过巨噬细胞消耗可导致神经损伤后的再生修复能力下降.
Clodronate liposome alleviates functional regeneration after peripheral nerve injury via depleting macrophages
Objective To investigate the role of macrophage depletion in functional regeneration after peripheral nerve injury.Methods Adult mice in the experimental group were intraperitoneally injected with the clodronate liposome to exhaust the macrophages and then were subjected a sciatic nerve crush injury model.The mice in the control group were administrated with the control liposome to replace the clodronate.Seven days post injury(dpi),immunofluorescence staining was performed to illustrate the F4/80 positive macrophages and the GAP43 positive regenerating axons.At 28 dpi,immunofluorescence staining was used to detect the F4/80 positive macrophages,behavior tests and neuroelectrophysiology were conducted to assay the motor function and nerve conduction.The wet weight of gastrocnemius muscle and their myofiber's size were measured to reflex the myoatrophy in the target muscles.Results The macrophages in the injured nerves were exhausted more than 70%at both 7 dpi and 28 dpi,and GAP43-positive regenerating axons in length at 7dpi were less and shorter in the experimental group than those of the control group.At 28 dpi,compared with the control group,the motor ability and nerve conduction intensity were significantly decreased,the latency of nerve conduction was prolonged,and the wet weight ratio and myofiber size were significantly reduced in the experimental group.Conclusions The clodronate liposome can alleviate the functional regeneration after peripheral nerve injury through exhausting macrophages.

MacrophageChlodronate liposomePeripheral nerve injuryFunctional regeneration

李云伦、许逸舟、蔡家乐、许淑怡、张家琪、傅兰雅、马心蕊、何叶、王祥海、郭家松

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南方医科大学基础医学院组织学与胚胎学教研室,广州 510515

南方医科大学珠江医院脊柱外科,广州 510510

广东省组织构建与检测重点实验室,广州 510515

巨噬细胞 氯膦酸盐 周围神经损伤 功能性修复

国家自然科学基金

82271393 & 82071386

2024

中国临床解剖学杂志
中国解剖学会

中国临床解剖学杂志

CSTPCD北大核心
影响因子:0.7
ISSN:1001-165X
年,卷(期):2024.42(3)