[Mechanism of "biaoben acupoint combination" electroacupuncture pretreatment in alleviating cardiomyocyte cuproptosis in rats with myocardial ischemia-reperfusion injury].
Wei Y, Zhang Y, et al. • Zhongguo zhen jiu = Chinese acupuncture & moxibustion • 2026
'Biaoben acupoint combination' EA pretreatment can attenuate the structural damage of cardiomyocytes and mitochondria, enhance the expression of mitochondrial respiratory chain complexes I-IV in MIRI rats, and alleviate MIRI by inhibiting elesclomol-induced cardiomyocyte cuproptosis.
Key Findings
Results
MIRI significantly increased cuproptosis-related protein expression and reduced mitochondrial respiratory chain complex activity compared to sham controls.
Compared with the Sham group, myocardial infarct area and protein expression of Cp, FDX1, DLST, and DLAT were all increased in the MIRI group (P<0.01)
Expression of mitochondrial respiratory chain complexes I-IV was decreased in the MIRI group compared to Sham (P<0.01)
MIRI model was established by ligation of the left anterior descending coronary artery in male SD rats
HE staining and transmission electron microscopy revealed disordered arrangement of myocardial mitochondria, mitochondrial edema, and mitochondrial outer membrane rupture in the MIRI group
Results
Electroacupuncture (EA) pretreatment at the 'biaoben acupoint combination' significantly reduced myocardial infarct area and cuproptosis marker proteins compared to the MIRI group.
Compared with the MIRI group, the EA group showed decreased myocardial infarct area and decreased protein expression of Cp, FDX1, DLST, and DLAT (P<0.01)
Expression of mitochondrial respiratory chain complexes I-IV was increased in the EA group compared to MIRI (P<0.01)
EA pretreatment was applied at bilateral Neiguan (PC6), bilateral Zusanli (ST36), and Guanyuan (CV4) with continuous wave at 2 Hz, 20 min per session, once daily for 7 consecutive days
Improvement in mitochondrial ultrastructure (disordered arrangement, edema, outer membrane rupture) was more pronounced in the EA group than in the EA+ES group
Results
Elesclomol (ES), a copper ionophore, partially antagonized the protective effects of EA pretreatment, confirming that EA acts through inhibition of cuproptosis.
Compared with the EA group, the EA+ES group showed increased myocardial infarct area and increased protein expression of Cp, FDX1, DLST, and DLAT (P<0.01, P<0.05)
Expression of mitochondrial respiratory chain complexes I-IV was decreased in the EA+ES group compared to the EA group (P<0.01)
Elesclomol was administered intraperitoneally at 5 mg/kg, 30 minutes before MIRI model establishment
The ES group alone showed increased Cp and FDX1 protein expression compared to the MIRI group (P<0.01), indicating enhanced cuproptosis signaling
Results
EA pretreatment combined with elesclomol (EA+ES) still showed some improvement in mitochondrial respiratory chain complex expression compared to MIRI alone, though attenuated versus EA alone.
Compared with the MIRI group, the EA+ES group showed increased mitochondrial respiratory chain complex I-IV expression (P<0.05)
Compared with the MIRI group, the EA+ES group showed decreased Cp, FDX1, DLST, and DLAT protein expression (P<0.01)
Mitochondrial ultrastructure improvements (disordered arrangement, edema, outer membrane rupture) were observed in the EA+ES group relative to MIRI and ES groups, but were less pronounced than in the EA group alone
The partial protective effect in EA+ES suggests EA pretreatment retains some cardioprotective mechanisms even when cuproptosis is pharmacologically provoked
Methods
The study used a five-group experimental design in male SD rats to dissect the role of cuproptosis in MIRI and EA-mediated cardioprotection.
70 male Sprague-Dawley rats were used; 10 in the Sham group and 15 in each of the MIRI, ES, EA, and EA+ES groups
Myocardial infarct area was measured by TTC staining; cardiomyocyte morphology by HE staining; mitochondrial ultrastructure by transmission electron microscopy
Mitochondrial respiratory chain complexes I-IV expression was measured by ELISA; Cp, FDX1, DLST, and DLAT protein expression by Western blot
Cuproptosis markers measured included ceruloplasmin (Cp), ferredoxin 1 (FDX1), dihydrolipoamide S-succinyltransferase (DLST), and dihydrolipoamide S-acetyltransferase (DLAT)
What This Means
This research investigated how a specific acupuncture technique—called 'biaoben acupoint combination' electroacupuncture (EA)—might protect the heart from damage that occurs when blood flow is restored after a heart attack, a phenomenon known as myocardial ischemia-reperfusion injury (MIRI). The study focused on a newly recognized form of cell death called 'cuproptosis,' which is triggered by excess copper inside cells and disrupts the energy-producing machinery of the cell (the mitochondria). Rats received EA pretreatment at acupuncture points Neiguan (PC6), Zusanli (ST36), and Guanyuan (CV4) for seven days before the heart injury was induced.
The researchers found that MIRI caused significant increases in cuproptosis-related proteins (Cp, FDX1, DLST, DLAT) and damaged mitochondrial function, as shown by reduced activity of respiratory chain complexes I-IV. EA pretreatment significantly reversed these effects: it reduced the size of the myocardial infarct, lowered cuproptosis marker proteins, improved mitochondrial structure, and restored respiratory chain complex activity. When a copper-loading drug (elesclomol) was given to artificially trigger cuproptosis and counteract EA's benefits, EA's protective effects were partially but not completely blocked, further confirming that EA works in part by suppressing this copper-mediated cell death pathway.
This research suggests that electroacupuncture pretreatment may protect heart tissue during reperfusion injury by reducing a specific type of cell death driven by copper toxicity in the mitochondria. The findings provide a mechanistic explanation for acupuncture's potential cardioprotective effects and identify cuproptosis as a possible therapeutic target in heart attack treatment. These results are from an animal study and further research would be needed to determine whether similar effects occur in humans.
Wei Y, Zhang Y, Wan X, Mao J, Wang S, Jiang C, et al.. (2026). [Mechanism of "biaoben acupoint combination" electroacupuncture pretreatment in alleviating cardiomyocyte cuproptosis in rats with myocardial ischemia-reperfusion injury].. Zhongguo zhen jiu = Chinese acupuncture & moxibustion. https://doi.org/10.13703/j.0255-2930.20250312-0001