昆明医科大学学报2025，Vol.46Issue(7)：38-45,8.DOI:10.12259/j.issn.2095-610X.S20250705
基于巨噬细胞自噬探讨川芎嗪对脊髓损伤修复的分子机制
Exploring the Molecular Mechanism of Ligustrazine in Spinal Cord Injury Repair Based on Macrophage Autophagy
摘要
Abstract
Objective To investigate the effect of ligustrazine on spinal cord repair from the perspective of macrophage autophagy and its molecular mechanism in a rat model.Methods A rat model of spinal cord injury was established using Allen's method.Successful modeling was indicated by hindlimb spasm,tail twisting,and Basso,Beattie,and Bresnahan(BBB)score of 0.The rats were divided into 4 groups:sham-operation group,model group,low-dose ligustrazine group,and high-dose ligustrazine group,with 10 rats in each group.The low-dose and high-dose ligustrazine groups were administered ligustrazine(150 mg/kg and 200 mg/kg,respectively)via intraperitoneal injection,while the normal and model groups received an equal volume of normal saline once daily for 28 days.At different time points after surgery,the hindlimb motor function of the rats was assessed using the BBB scale.Hematoxylin-eosin(HE)and Nissl staining were used to observe the histopathological changes in the spinal cord tissue and the morphology of neurons.Enzyme-linked immunosorbent assay(ELISA)was employed to detect the expression levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in the spinal cord tissue.TUNEL staining was used to evaluate the apoptosis status of spinal cord neurons.Protein levels of LC3 I,LC3 Ⅱ,Bax,and Bcl-2 in the spinal cord tissue were detected by Western Blot.Electron microscopy was used to observe the formation of autophagosomes in spinal cord macrophages,and immunofluorescence was used to detect the protein expression of LC3 Ⅱ in spinal cord macrophages.Results Compared with the sham-operation group,the model group exhibited impaired hindlimb function and spinal cord tissue morphology(P<0.05),along with decreased levels of SOD,apoptosis,LC3 Ⅱ/Ⅰ,Bcl-2 protein expression,autophagosome number in macrophages,and LC3 Ⅱ protein expression,as well as increased levels of MDA,Bax,and Bax/Bcl-2 protein expression(P<0.05).Compared with the model group,both the low-dose and high-dose ligustrazine groups showed improved hindlimb function and spinal cord tissue morphology(P<0.05),with increased levels of SOD,apoptosis,LC3 Ⅱ/Ⅰ,Bcl-2 protein expression,autophagosome number in macrophages,and LC3 Ⅱ protein expression,as well as decreased levels of MDA,Bax,and Bax/Bcl-2 protein expression(P<0.05).The intervention effect of ligustrazine was dose-dependent.Conclusion Ligustrazine can effectively repair spinal cord injury in rats,and its molecular mechanism may be related to the activation of autophagy in spinal cord macrophages and the inhibition of neuronal apoptosis.关键词
川芎嗪/脊髓损伤/巨噬细胞/自噬/细胞凋亡Key words
Ligustrazine/Spinal cord injury/Macrophages/Autophagy/Apoptosis分类
医药卫生引用本文复制引用
宋希猛,袁士龙,卢子昂,徐茂通..基于巨噬细胞自噬探讨川芎嗪对脊髓损伤修复的分子机制[J].昆明医科大学学报,2025,46(7):38-45,8.基金项目
山东省医药卫生科技项目(2024030124031Q) （2024030124031Q）
济宁市重点研发计划项目(2024YXNS222) （2024YXNS222）
