Electroacupuncture improves myocardial injury in rats with acute myocardial ischemia by inhibiting HPA axis hyperactivity via modulating hippocampal glutamatergic system

doi:10.12122/j.issn.1673-4254.2025.08.04

Abstract

Abstract:

Objective To clarify the role of hippocampal glutamate system in regulating HPA axis in mediating the effect of electroacupuncture (EA) at the heart meridian for improving myocardial injury in rats with acute myocardial ischemia (AMI). Methods Male SD rats were randomized into sham-operated group, AMI group, EA group, and L-glutamic acid+EA group (n=9). Rat models of AMI were established by left descending coronary artery ligation, and EA was applied at the "Shenmen-Tongli" segment; the rats in L-glutamic acid+EA group were subjected to microinjection of L-glutamic acid into the bilateral hippocampus prior to AMI modeling and EA treatment. Cardiac functions of the rats were evaluated using echocardiography, and ECG and heart rate variation (HRV) were analyzed using PowerLab and LabChart. Pathological changes in the myocardial tissue was examined using HE staining, and serum levels of myocardial enzymes were detected with ELISA. Myocardial expressions of TH and GAP43 were detected with immunohistochemistry, and colocalization of VGLUT1, VGLUT2 and c-fos were observed using immunofluorescence staining; the expressions of VGLUT1, VGLUT2, NMDAR1 and NMDAR2B were detected using Western blotting. Results The rat models of AMI showed significantly decreased LVEF and LVFS and increased serum levels of myocardial enzymes in positive correlation with the HPA axis. Numerous TH- and GAP43-positive cells were observed in the hippocampus, where the expressions of NE and E, neurons colabeled with VGLUT1, VGLUT2 and c-fos, and expressions of VGLUT1, VGLUT2, NMDAR1, NMDAR2B and Glu increased significantly. All these changes were significantly improved by interventions with EA as compared with those in AMI and L-Glutamate+EA groups. Conclusion In rats with AMI, EA at the heart meridian can regulate excessive glutamate release in the hippocampus, thereby inhibiting HPA axis hyperactivity and reducing sympathetic nerve activity to protect the myocardial tissue.

Key words: myocardial ischemia, electroacupuncture, hippocampus, HPA axis, glutamate

Kun WANG, Haiyan ZUO, Jiaojiao ZHANG, Xin WU, Wenhui WANG, Shengbing WU, Meiqi ZHOU. Electroacupuncture improves myocardial injury in rats with acute myocardial ischemia by inhibiting HPA axis hyperactivity via modulating hippocampal glutamatergic system[J]. Journal of Southern Medical University, 2025, 45(8): 1599-1607.

Figures/Tables 9

Fig.1 Echocardiography of the rats in the 4 groups. **P<0.01 vs Sham group; ##P<0.01 vs Model group; ∆P<0.05, ∆∆P<0.01 vs EA group.

Fig.2 Serum levels of CK-MB and cTnT of the rats. **P<0.01 vs Sham group; ##P<0.01 vs Model group; ∆P<0.05, ∆∆P<0.01 vs EA group.

Fig.3 Pathological changes in the myocardial tissue of the rats (HE staining, scale bar=50 μm).

Fig.4 Serum levels of CRH and CORT of the rats. **P<0.01 vs Sham group; ##P<0.01 vs Model group; ∆∆P<0.01 vs EA group.

Fig.5 Heart rate variability of the rats. **P<0.01 vs Sham group; ##P<0.01 vs Model group; ∆∆P<0.01 vs EA group. LF: Low frequency; HF: High frequency.

Fig.6 Expressions of TH and GAP 43 in the myocardial tissue of the rats (Immunofluorescence staining, scale bar=20 μm). **P<0.01 vs Sham group; ##P<0.01 vs Model group; ∆∆P<0.01 vs EA group.

Fig.7 Serum levels of NE and E of the rats. **P<0.01 vs Sham group; ##P<0.01 vs Model group; ∆∆P<0.01 vs EA group.

Fig.8 Colocalization of VGLUT1, VGLUT2, and c-fos in rat hippocampus in different groups (immunofluorescence staining, scale bar=20 μm). **P<0.01 vs Sham group; ##P<0.01 vs Model group; ∆∆P<0.01 vs EA group.

Fig.9 Expressions of VGLUT1, VGLUT2, NMDAR1, NMDAR2B and Glu in the hippocampus of the rats. **P<0.01 vs Sham group; #P<0.05, ##P<0.01 vs Model group; ∆∆P<0.01, ∆P<0.05 vs EA group.

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