南方医科大学学报

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (8): 1599-1607.doi: 10.12122/j.issn.1673-4254.2025.08.04

• • 上一篇    

电针通过调控海马谷氨酸释放抑制HPA轴亢进从而改善急性心肌缺血大鼠的心肌损伤

王堃1,2(), 左海燕2, 张娇娇2, 吴欣2, 王文慧2, 吴生兵2, 周美启2()   

  1. 1.安徽中医药大学，中西医结合博士后流动站，安徽 合肥 230012
    2.安徽中医药大学，经脉脏腑相关安徽省重点实验室，安徽 合肥 230012
  • 收稿日期:2025-04-01 出版日期:2025-08-20 发布日期:2025-09-05
  • 通讯作者: 周美启 E-mail:ahwk0819@ahtcm.edu.cn;meiqizhou@163.com
  • 作者简介:王 堃，博士后在站，E-mail: ahwk0819@ahtcm.edu.cn
  • 基金资助:
    国家自然科学基金(82004462);国家自然科学基金(82274303);安徽高校自然科学研究重点项目(2023AH050806);安徽高校自然科学研究重点项目(2023AH050862)

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

Kun WANG1,2(), Haiyan ZUO2, Jiaojiao ZHANG2, Xin WU2, Wenhui WANG2, Shengbing WU2, Meiqi ZHOU2()   

  1. 1.Postdoctoral Research Station of Integrated Traditional and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China
    2.Anhui Provincial Key Laboratory of Meridian Viscera Correlationship, Anhui University of Chinese Medicine, Hefei 230012, China
  • Received:2025-04-01 Online:2025-08-20 Published:2025-09-05
  • Contact: Meiqi ZHOU E-mail:ahwk0819@ahtcm.edu.cn;meiqizhou@163.com
  • Supported by:
    National Natural Science Foundation of China(82004462)

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摘要：

目的 验证海马谷氨酸（Glu）能系统介导调控下丘脑-垂体-肾上腺轴（HPA）在电针心经改善急性心肌缺血（AMI）大鼠心肌损伤中的作用。 方法 雄性SD大鼠随机分成4组，分别为假手术组（Sham）、模型组（Model）、针刺组（EA）及L-谷氨酸+针刺组（Glu+EA），9只/组。采用左冠状动脉前降支结扎法制备AMI模型，并选择“神门-通里”段进行电针治疗。其中Glu+EA组在海马双侧注射L-谷氨酸的基础上复制AMI模型后予以电针治疗。采用心动超声左室射血分数（LVEF）、左室短轴缩短指数（LVFS）评估心功能，PowerLab记录心电图，LabChart分析心率变异性（HRV）中频域指标低频功率（LF）和高频功率（HF）及LF/HF比值变化，HE染色法检测心肌组织病理学变化，ELISA法检测血清肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白（cTnT）、促肾上腺皮质激素释放激素（CRH）、皮质醇（CORT）、去甲肾上腺素（NE）、肾上腺素（E）及海马Glu含量，免疫组化染色观察心肌酪氨酸羟化酶（TH）、生长相关蛋白-43（GAP 43）的阳性表达，免疫荧光染色观察海马囊泡谷氨酸转运蛋白1（VGLUT1）、囊泡谷氨酸转运蛋白2（VGLUT2）和原癌基因蛋白（c-fos）共定位，Western Blotting检测海马VGLUT1、VGLUT2、N-甲基-D-天门冬氨酸受体1（NMDAR1）、N-甲基-D-天冬氨酸受体2B（NMDAR2B）蛋白表达。 结果 与Sham组比较，Model组大鼠LVEF、LVFS降低（P<0.01），心肌酶CK-MB、cTnT含量增加（P<0.01），HE染色观察到心肌组织明显的细胞水肿、心肌纤维排列紊乱及炎性细胞广泛浸润，HPA轴激素CRH、CORT含量明显增加（P<0.01），且与心肌酶呈正相关，与LVEF、LVFS呈负相关（P<0.01），HRV中HF比值降低，LF比值与LF/HF升高（P<0.01），交感神经活性标记物TH、GAP 43的阳性神经纤维分布增加，儿茶酚胺递质NE、E表达升高（P<0.01），海马VGLUT1、VGLUT2与c-fos共定位的阳性细胞数量增加（P<0.01），VGLUT1、VGLUT2、NMDAR1、NMDAR2B蛋白及Glu递质水平升高（P<0.01）；与Model组和Glu+EA组比较，EA组大鼠LVEF、LVFS均升高（P<0.01，P<0.05），心肌酶水平降低（P<0.05，P<0.01），心肌组织病理损伤程度减轻，HF比值升高，LF比值与LF/HF降低（P<0.01），交感神经活性标记物的阳性神经纤维分布降低，儿茶酚胺类递质及HPA轴激素表达均减少（P<0.01），海马VGLUT1、VGLUT2与c-fos共定位的阳性细胞数量减少（P<0.01），Glu递质及受体表达明显降低（P<0.01，P<0.05）。 结论 电针心经可能通过调控海马谷氨酸释放，抑制HPA轴过度亢进，从而调节交感神经活性，达到保护心肌的作用。

关键词: 心肌缺血, 电针, 海马, HPA轴, 谷氨酸

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