中国中药杂志2026，Vol.51Issue(8)：2359-2366,8.DOI:10.19540/j.cnki.cjcmm.20251112.401
无忧汤通过RhoA/ROCK1/Drp1通路对慢性睡眠剥夺模型大鼠海马神经元细胞凋亡及线粒体损伤的影响
Effects of Wuyou Decoction on hippocampal neuronal apoptosis and mitochondrial damage in chronic sleep deprivation rats via RhoA/ROCK1/Drp1 pathway
摘要
Abstract
This study investigated the protective effects and underlying mechanisms of Wuyou Decoction(WYD)against hippocampal neuronal apoptosis and mitochondrial damage in a rat model of chronic sleep deprivation(CSD).Fifty male Sprague-Dawley(SD)rats were randomly assigned to the following groups:normal,model,and WYD low-,medium-,and high-dose groups(WYD-L,WYD-M,WYD-H),respectively.Except the normal group,CSD was induced in other groups using the horizontal platform sleep deprivation method,which included 7 days of adaptive modeling followed by 21 days of formal modeling.Intragastric administration of WYD was initiated concurrently with the formal modeling phase and maintained for 28 days.Learning and memory abilities were assessed using the Morris water maze test.The morphological and quantitative changes of hippocampal neurons were evaluated by hematoxylin-eosin(HE)staining,Nissl staining,and neuron-specific nuclear protein(NeuN)immunohistochemistry.Mitochondrial ultrastructure was examined by transmission electron microscopy,and adenosine triphosphate(ATP)content in the hippocampus was measured with a commercial assay kit.Western blot was employed to detect apoptosis-related proteins B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),caspase-3,cleaved caspase-3,cytochrome C(Cyt C),as well as Ras homolog family member A(RhoA),Rho-associated protein kinase 1(ROCK1),dynamin-related protein 1(Drp1),and p-Drp1(Ser616)in hippocampal tissues.Molecular docking was used to evaluate the interactions between active components of WYD and pathway-related proteins.The results revealed that,compared to the normal group,the model group showed significant cognitive impairment,neuronal damage,reduced neuronal count,and abnormal mitochondrial structure,including disrupted cristae and myelin-like figures.The ATP content decreased,along with increased Cyt C release,upregulation of Bax and cleaved caspase-3/caspase-3,downregulation of Bcl-2,and activation of the RhoA/ROCK1/Drp1 signaling pathway.In contrast,the WYD-M group exhibited improved cognitive performance,restored neuronal morphology and quantity,and alleviated mitochondrial damage,while the ATP levels also increased.Furthermore,WYD-M treatment significantly suppressed Cyt C release,downregulated Bax and cleaved caspase-3/caspase-3 expression,upregulated Bcl-2,and effectively inhibited the activation of the RhoA/ROCK1/Drp1 signaling pathway.Molecular docking indicated that paeoniflorin and ferulic acid,the primary active components of WYD,had strong binding affinities with the key proteins in the RhoA/ROCK1/Drp1 signaling pathway,with binding energies all below-5 kcal·mol-1.In conclusion,WYD may protect mitochondrial integrity,reduce Cyt C release,inhibit hippocampal neuronal apoptosis,and ultimately improve cognitive function in CSD model rats potentially by suppressing the RhoA/ROCK1/Drp1 signaling pathway.关键词
无忧汤/慢性睡眠剥夺/神经元细胞凋亡/线粒体损伤/RhoA/ROCK1/Drp1 信号通路Key words
Wuyou Decoction/chronic sleep deprivation/neuronal apoptosis/mitochondrial damage/RhoA/ROCK1/Drp1 signa-ling pathway引用本文复制引用
何丽玲,赖碧璇,吴丹,牛绮萱,龙清华,王政喻..无忧汤通过RhoA/ROCK1/Drp1通路对慢性睡眠剥夺模型大鼠海马神经元细胞凋亡及线粒体损伤的影响[J].中国中药杂志,2026,51(8):2359-2366,8.基金项目
湖北省自然科学基金联合基金项目(2023AFD068) （2023AFD068）
湖北省中医药管理局中医药科研项目(ZY20230047) （ZY20230047）
湖北民族大学校内科研项目(XN2316) （XN2316）
湖北民族大学研究生创新项目(MYK2023060) （MYK2023060）
