中药新药与临床药理2025，Vol.36Issue(5)：674-682,9.DOI:10.19378/j.issn.1003-9783.2025.05.003
基于SIRT1/AMPK通路探讨虎杖苷对臂丛神经根性撕脱伤大鼠神经再生与功能恢复的作用及机制
Exploring the Effect and Mechanism of Polydatin on Nerve Regeneration and Functional Recovery in Rats with Brachial Plexus Root Avulsion Injury Based on the SIRT1/AMPK Pathway
摘要
Abstract
Objective To explore the effect and mechanism of polydatin on nerve regeneration and functional recovery in rats with brachial plexus root avulsion(BPRA)injury based on the SIRT1/AMPK pathway.Methods Sixty SD rats were randomly divided into five groups:sham-operation group,model group,low-dose polydatin group,high-dose polydatin group,and SIRT1 inhibitor group,with 12 rats in each group.The BPRA rat model was established by surgically avulsing the C5-C7 spinal nerve roots and replanting the C6 nerve root.After BPRA surgery,the low-and high-dose polydatin groups were intraperitoneally injected with polydatin at doses of 20 and 40 mg·kg-1,respectively,while the SIRT1 inhibitor group was intraperitoneally injected with polydatin 40 mg·kg-1+SIRT1 inhibitor(EX527)5 mg·kg-1,once daily for 8 consecutive weeks.The Terzis grooming test(TGT)was used to evaluate the recovery of motor function in rats.Retrograde labeling of motor neurons in the spinal cord tissue was performed using Fluoro-Gold.The expression level of choline acetyltransferase(ChAT)in the spinal cord tissue was detected by immunofluorescence.Pathological changes in the biceps brachii muscle were observed using HE staining.The protein expression levels of SIRT1,AMPK,LC3,and p62 in the spinal cord tissue were detected by Western Blot.Results There was no significant difference in body mass among the groups(P＞0.05).Compared with the sham-operation group,the TGT score of the model group was significantly decreased(P＜0.01).The biceps brachii muscle fibers in the model group were smaller in diameter,with more fibroblasts and significant muscle atrophy,and the wet mass ratio of the injured/healthy side of the biceps brachii was significantly decreased(P＜0.01).The number of Fluoro-Gold-labeled motor neurons and ChAT-positive neurons in the anterior horn of the spinal cord was significantly reduced(P＜0.05,P＜0.01).The protein expression of p62 in the spinal cord tissue was significantly up-regulated(P＜0.01),while the protein expressions of LC3Ⅱ/LC3Ⅰ,SIRT1,and AMPK were significantly down-regulated(P＜0.05).Compared with the model group,the TGT score of the high-dose polydatin group began to increase significantly from the third week after surgery(P＜0.01),and the TGT score of the low-dose polydatin group began to increase significantly from the sixth week after surgery(P＜0.01).In the low-and high-dose polydatin groups,the cross-sectional area of the biceps brachii muscle fibers was significantly increased,the muscle cell nuclei were clear,and the muscle fiber morphology was closer to that of the sham-operation group.The wet mass ratio of the injured/healthy side of the biceps brachii was significantly increased(P＜0.01),and the number of Fluoro-Gold-labeled motor neurons and ChAT-positive neurons in the anterior horn of the spinal cord was significantly increased(P＜0.01).The protein expression of p62 in the spinal cord tissue was significantly down-regulated(P＜0.01),while the protein expression of AMPK was significantly up-regulated(P＜0.05).In the high-dose polydatin group,the protein expressions of LC3Ⅱ/LC3Ⅰ and SIRT1 in the spinal cord tissue were significantly up-regulated(P＜0.05,P＜0.01).Compared with the high-dose polydatin group,the TGT score of the SIRT1 inhibitor group was significantly decreased(P＜0.01),the wet mass ratio of the injured/healthy side of the biceps brachii was significantly decreased(P＜0.01),and the number of Fluoro-Gold-labeled motor neurons and ChAT-positive neurons in the anterior horn of the spinal cord was significantly reduced(P＜0.01).The protein expressions of LC3Ⅱ/LC3Ⅰ,SIRT1,and AMPK in the spinal cord tissue were significantly down-regulated(P＜0.01).Conclusion Polydatin can promote the recovery of motor function,improve muscle atrophy,and enhance motor neuron survival and axonal regeneration in rats with BPRA.Its mechanism may be related to the activation of the SIRT1/AMPK pathway to promote autophagy and inhibit motor neuron death.关键词
虎杖苷/臂丛神经根性撕脱伤/SIRT1/AMPK通路/自噬/运动神经元/大鼠Key words
polydatin/brachial plexus root avulsion injury/SIRT1/AMPK pathway/autophagy/motor neurons/rats分类
医药卫生引用本文复制引用
加彩菊,黄豆豆,陈曼妮,程晓民,张琴,张勰..基于SIRT1/AMPK通路探讨虎杖苷对臂丛神经根性撕脱伤大鼠神经再生与功能恢复的作用及机制[J].中药新药与临床药理,2025,36(5):674-682,9.基金项目
广东省基础与应用基础研究基金项目(2021A1515110800) （2021A1515110800）
广东省中医药局科研项目(20241084). （20241084）
