[Acupuncture inhibits cuproptosis to prolong the time window of thrombolysis by down-regulating cerebral FDX1 and DLAT in rats with cerebral infarction].

OBJECTIVES: To observe the effect of acupuncture on neuronal cuproptosis after thrombolytic treatment in rats with cerebral infarction (CI), so as to explore its underlying mechanisms in prolonging the time window of thrombolysis therapy for CI. METHODS: In the first part of the present study, 40 male SD rats were randomly divided into 5 groups:sham operation, model, 4.5 h thrombolysis, 6 h thrombolysis and acupuncture+6 h thrombolysis groups, with 8 rats in each group. The CI model was prepared by modified autologous thromboembolism method. Rats of the 4.5 h thrombolysis, 6 h thrombolysis and acupuncture+6 h thrombolysis groups received thrombolysis with intravenous injection of recombinant human tissue plasminogen activator (rt-PA, 10 mg/kg) through tail vein at 4.5 h or 6 h after modeling. Manual acupuncture stimulation was applied to bilateral "Neiguan"(PC6) and "Shuigou"(CV26) at the same time with thrombolysis administration for rats of the acupuncture+6 h thrombolysis group, with the needles retained for 30 min. The cerebral blood flow was monitored using laser diffusion blood flow imaging, and neurological deficit score was evaluated 2 h and 24 h after successful modeling using Bederson's method. The CI volume was observed after triphenyltetrazole chloride staining. The immunoactivity of neuronal nuclei(NeuN) in the ischemic penumbra (IP) region of the cerebral cortex was detected by immunofluorescence staining. In the second part of the study, 24 male SD rats were randomly divided into sham operation group, model group, 6 h thrombolysis group and acupuncture+6 h thrombolysis group, with 6 rats in each group. The protein and mRNA relative expression levels of Ferredoxin-1 (FDX1) and dihydrolipoamide acetyltransferase (DLAT) in the IP region of the right cerebral cortex were detected by Western blot and real-time PCR, separately. The copper ion, pyruvate and adenosine triphosphate (ATP) contents in the IP area of the cerebral cortex tissue were detected using colorimetry. RESULTS: <0.01). CONCLUSIONS: Acupuncture can prolong the time window of thrombolysis therapy for CI rats, which may be related to its function in down-regulating the protein and mRNA expressions of FDX1 and DLAT in ischemic cerebral cortex.