世界中医药2026，Vol.21Issue(4)：636-643,8.DOI:10.3969/j.issn.1673-7202.2026.04.009
温阳复元方抑制脑缺血再灌注大鼠神经元坏死性凋亡和线粒体分裂
Mechanisms of Wenyang Fuyuan Formula in Inhibiting Neuronal Necroptosis and Mitochondrial Fission in Rats with Cerebral Ischemia-reperfusion Injury
摘要
Abstract
Objective:To elucidate the mechanisms of the Wenyang Fuyuan Formula in treating cerebral ischemia-reperfusion inju-ry(CIRI)in rats by detecting indicators related to the receptor-interacting protein kinase 1(RIPK1)/mixed lineage kinase domain-like protein(MLKL)/phosphoglycerate mutase 5(PGAM5)signaling pathway.Methods:Rats were randomly divided into a sham-operation group,model group,necrostatin-1(Nec-1)group,and Wenyang Fuyuan Formula group using a random number table.A rat CIRI model was established using the filament occlusion method.After one week of intervention with Wenyang Fuyuan Formula or Nec-1,2,3,5-triphenyltetrazolium chloride(TTC)staining was performed to determine successful model establishment.Neuro-logical deficits were evaluated using the Bederson scoring system.Hematoxylin-eosin(HE)staining and Nissl staining were used to observe the extent of brain tissue damage.Immunofluorescence was used to detect the expression of RIPK1 and PGAM5.Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and Western blot(WB)were used to detect the mRNA and protein expression levels of RIPK1,RIPK3,MLKL,PGAM5,and Drp1.Results:Compared with the sham-operation group,rats in the model group exhibited obvious white infarct areas in brain tissue,increased Bederson scores(P＜0.05),and severe brain tissue damage.Nissl staining showed increased neuronal apoptosis(P＜0.05),and the mRNA and protein expression levels of RIPK1,RIPK3,MLKL,PGAM5,and Drp1 in brain tissue were significantly increased(P＜0.05).Compared with the model group,rats in the Nec-1 group and the Wenyang Fuyuan Formula group showed smaller infarct areas,lower Bederson scores(P＜0.05),more Nissl bodies,and reduced neuronal apoptosis in brain tissue.The mRNA and protein expression levels of RIPK1,RIPK3,MLKL,PGAM5,and Drp1 were significantly decreased(P＜0.05),with a more pronounced reduction in the Wenyang Fuyuan Formula group.Conclusion:The Wenyang Fuyuan Formula may exert neuroprotective effects by downregulating the expression of proteins related to the RIPK1/MLKL/PGAM5 signaling pathway in CIRI rats,reducing mitochondrial fission,and further inhibiting neuronal necroptosis,thereby alleviating cellular damage.关键词
脑缺血再灌注损伤/受体相互作用蛋白激酶1/混合谱系激酶结构域样蛋白/磷酸甘油酸变位酶5信号通路/神经元/坏死性凋亡/线粒体分裂/温阳复元方/作用机制/大鼠模型Key words
Ischemia-reperfusion injury/RIPK1/MLKL/PGAM5 signaling pathway/Neuron/Necroptosis/Mitochondrial fission/Wenyang Fuyuan Formula/Mechanism of action/Rat model分类
医药卫生引用本文复制引用
周珂青,张鼎,孙春英,姜明贺,李方存,胡跃强..温阳复元方抑制脑缺血再灌注大鼠神经元坏死性凋亡和线粒体分裂[J].世界中医药,2026,21(4):636-643,8.基金项目
国家自然科学基金项目(82260904) （82260904）
国家中医药管理局高水平重点学科-中医内科学(ZYYZDXK-2023166) （ZYYZDXK-2023166）
广西中医脑病临床研究中心项目(桂科AD20238028) （桂科AD20238028）
广西中医药大学"岐黄工程"高层次人才团队(202410) （202410）
广西中医药重点学科建设项目(GZXK-Z-20-13). （GZXK-Z-20-13）
