海南医科大学学报2026，Vol.32Issue(13)：979-985,7.DOI:10.13210/j.cnki.jhmu.20250709.003
HSP90/MLKL/PGAM5/DRP1通路调控线粒体动力学抗VaD的作用研究
Study on the regulatory role of the HSP90/MLKL/PGAM5/DRP1 pathway in mitochondrial dynamics against vascular dementia
摘要
Abstract
Objective:To explore the neuroprotective mechanism of the HSP90/MLKL/PGAM5/DRP1 pathway in vascular dementia(VaD)by regulating the balance of mitochondrial dynamics.Methods:SD rats were randomly divided into sham opera-tion control group,model group and HSP90 inhibitor intervention group by random number table method,with 9 rats in each group.The spatial learning and memory ability of rats was evaluated by the Morris water maze positioning navigation test system.The morphological changes of neurons in the hippocampal CA1 area were observed by combining H&E staining technology.Se-rum Tumor Necrosis Factor-α(TNF-α)was applied by ELISA.The levels of TNF-α and Interleukin-10(IL-10).Western blot was used to detect the expressions of proteins related to the HSP90/MLKL/PGAM5/DRP1 pathway,ATP synthase α subunit(ATP5A),fusion protein 1(MFN1),and fusion protein2(MFN2)in hippocampal tissues.Immunohistochemistry was used to detect the positive expression of p-MLKL.Results:Compared to the sham operation group,the escape latency of rats in the mod-el group was significantly prolonged,the number of crossing platforms was significantly reduced,and obvious neuronal damage was shown in the hippocampal tissue.The level of serum TNF-α increased and the level of IL-10 decreased(P<0.05);The pro-tein levels of HSP90 and PGAM5,the ratio of p-MLKL/MLKL,and the ratio of p-DRP1(ser616)/DRP1 in hippocampal tissue increased,while the protein levels of ATP5A,MFN1,and MFN2 decreased.Meanwhile,the number of P-MLKL positive cells increased significantly(P<0.05).After intervention with HSP90 inhibitors,all the above indicators could be significantly reversed(P<0.05),the pathological damage of hippocampal tissue was alleviated,and the learning and memory abilities were significantly improved.Conclusion:By inhibiting the HSP90/MLKL/PGAM5/DRP1 signaling pathway,it can reduce mitochondrial hyperdi-vision in VaD rats,maintain mitochondrial dynamic balance,inhibit neuroinflammation and improve cognitive function,providing a new target for the treatment of VaD.关键词
血管性痴呆/HSP90/MLKL/PGAM5/DRP1通路/线粒体动力学Key words
Vascular dementia/HSP90/MLKL/PGAM5/DRP1 pathway/Mitochondrial dynamics分类
医药卫生引用本文复制引用
朱小敏,陈炜,卓桂锋,符钰岚,劳祎林,黄颖睿,袁炳茂,吴林..HSP90/MLKL/PGAM5/DRP1通路调控线粒体动力学抗VaD的作用研究[J].海南医科大学学报,2026,32(13):979-985,7.基金项目
This study was supported by the National Natural Science Foundation of China(82374387,82160885) （82374387,82160885）
Guangxi University of Chinese Medicine"Qihuang Project"High-Level Talent Team(202410) （202410）
Guangxi Graduate Education Innovation Program(YCBZ2025190) （YCBZ2025190）
Guangxi High-Level Innovation Team and Outstanding Scholar Program(Guigao Talent[2020]No.6) （Guigao Talent[2020]No.6）
Guangxi Key Disciplines Construction Project of Traditional Chinese Medicine(GZXK-Z-20-13) 国家自然科学基金(82374387,82160885) （GZXK-Z-20-13）
广西中医药大学"歧黄工程"高层次人才团队(202410) （202410）
广西研究生教育创新计划项目(YCBZ2025190) （YCBZ2025190）
广西高等学校高水平创新团队及卓越学者计划(桂教人才[2020]6号) （桂教人才[2020]6号）
广西中医药重点学科建设项目(GZXK-Z-20-13) （GZXK-Z-20-13）
