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第46卷第9期 吴法然，孙书宏，葛 新. 铜元素体内代谢机制及其在相关疾病中的作用与治疗潜力［J］.
2026年9月 南京医科大学学报（自然科学版），2026，46（9）：1366-1382 ·1375 ·

表1 铜相关疾病病理及其发病机制
Table 1 Pathology and pathogenesis of copper⁃related diseases
Disease category Disease Pathology Molecular pathogenesis
Hepatic Non⁃alcoholic fatty ① Hepatic fat accumulation； Copper homeostasis imbalance：copper deficiency
dysfunction liver disease（NAFLD） ② Potential progression to liver cirrho⁃ inhibits fatty acid β⁃oxidation，promotes lipogene⁃
sis and hepatocellular carcinoma； sis，induces oxidative stress，inflammation and
③ Copper deficiency in patients insulin resistance；high fructose intake reduces
copper absorption
Neurodegenera⁃ Alzheimer’s disease ① Presence of amyloid plaques and neu⁃ Copper homeostasis imbalance：excess copper
tive diseases （AD） rofibrillary tangles in the gray matter； promotes Aβ peptide and Tau protein aggrega⁃
② High copper concentration in senile tion，activates inflammatory pathways，impairs
plaques Aβ clearance capacity，and enhances neurotoxi⁃
city
Amyotrophic lateral ① Selective degeneration of motor neu⁃ Copper homeostasis disorder：abnormal mito⁃
sclerosis（ALS） rons muscle weakness and atrophy； chondrial copper transport，insufficient copper
② ALS associated predominantly with binding of mutant SOD1 protein enhances neuro⁃
SOD1 gene mutations toxicity，and cerebrospinal fluid copper levels
are elevated in some patients
Cardiovascular Atherosclerosis ① Lipid deposition and inflammatory Copper modulates disease progression by regu⁃
disease response in the vascular intima； lating LDL oxidation，VSMC proliferation and in⁃
② Vascular occlusion； flammatory pathways；dietary copper deficiency
③ Association between plaque stability or excess increases disease risk，and copper
heterogeneity and copper content levels vary across different disease stages

Stroke ① Elevated serum copper in ischemic Copper，as an enzymatic cofactor，protects cere⁃
stroke； bral blood vessels；excess copper inhibits angio⁃
② Decreased serum copper in hemor⁃ genic cell functions，impairs lipid metabolism
rhagic stroke； and exacerbates ischemic stroke
③ Cerebrovascular injury and cerebral
tissue ischemia⁃hypoxia
Heart failure（HF） ① Myocardial dysfunction； Copper deficiency causes abnormal mitochondrial
② Impaired mitochondrial energy con⁃ CCO function，and disturbed copper transport
version capacity； impairs myocardial function；elevated serum cop⁃
③ Frequent comorbidity association per and Cu/Zn ratio are associated with in⁃
creased disease risk
Hereditary neu⁃ Menkes disease（MD） ① X⁃linked recessive inheritance； ATP7A gene mutation causes intestinal copper
ropathy ② Systemic copper deficiency through⁃ absorption disorder，reduces the activity of cop⁃
out the body； per ⁃ dependent enzymes，and induces neurode⁃
③ Multiple system abnormalities involv⁃ generation，cardiovascular malformations and
ing the nervous，cardiovascular and con⁃ connective tissue abnormalities
nective tissues
Wilson’s disease ① Autosomal recessive inheritance； ATP7B gene mutation impairs copper excretion；
（WD） ② Significantly elevated hepatic copper copper accumulation inhibits nuclear receptor
content； function，damages mitochondrial structure and
③ Abnormal mitochondrial morphology； function，and induces oxidative stress and cell
④ Possible manifestations of liver fail⁃ apoptosis
ure；
⑤ Hepatitis or neurological symptoms
Huntington’s disease ① Autosomal dominant inheritance； Abnormally elevated striatal copper promotes
（HD） ② Striatal and cerebral cortical atrophy； mutant HTT protein aggregation，inhibits mito⁃
③ Loss of psychiatric，cognitive and mo⁃ chondrial dehydrogenases，impairs lactate metabo⁃
tor functions lism，and exacerbates neurodegeneration