中药调控线粒体自噬防治血管性痴呆研究进展OA

Vascular dementia(VD)is a chronic cognitive impairment syndrome induced by cerebrovascular diseases.Its core pathogen-ic mechanisms consist of chronic cerebral hypoperfusion,oxidative stress,neuroinflammation and neuronal apoptosis.As a core mecha-nism for mitochondrial quality control,mitophagy plays a vital role in the pathogenesis,prevention and treatment of VD.Chinese medici-nals possess unique superiorities including multi-target effects,bidirectional regulatory properties and holistic therapeutic concepts.Chi-nese medicinals can accurately modulate mitophagy by activating multiple signaling pathways such as PINK1/Parkin,HIF1α/BNIP3 and PI3K/AKT/mTOR.This regulatory effect promotes the clearance of intracellular damaged mitochondria,alleviates oxidative stress,inhibits neuroinflammation and reduces neuronal apoptosis,so as to exert neuroprotective effects and improve learning and memory func-tions.Active monomeric constituents of Chinese medicinals,including Trillium tschonoskii total saponins(TTTS),quercetin,and myris-ticin lignans,as well as some classical compound formulas such as Chinese Angelica Blood-Supplementing Decoction,Kidney-Nourishing and Blood-Activating Formula,Channel-Unblocking and Orifice-Opening Pills,Minor Dingzhi Pills,all exert favorable regulatory effects on mitophagy.However,existing research still has certain limitations:(1)Most existing studies only focus on static correlations of pro-tein expression,lacking in-depth research on dynamic post-translational modification events represented by protein phosphorylation;(2)Clinical research evidence remains insufficient,and high-quality clinical trials are still scarce to validate the dose-response relationship between mitophagy modulation mediated by Chinese medicinals and clinical therapeutic efficacy in patients with VD;(3)The precise network mechanisms underlying the synergistic modulation of multiple signaling pathways by multi-ingredient Chinese medicinals remain incompletely elucidated.Although the mechanistic resolution of existing research remains inadequate,the integration and innovative de-velopment of interdisciplinary technologies are expected to further decipher the underlying molecular mechanisms and exploit the unique strengths of TCM in the prevention and treatment of VD.This will provide more effective TCM therapeutic strategies to tackle the VD crisis driven by population aging.