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杏仁核谷氨酸受体对创伤后应激障碍模型大鼠心血管功能的作用

吴亚洋^1,2, 蔡坤宜^1,2, 吴雨洁^1,2, 郑超³, 汪萌芽², 张环环^1,*

¹皖南医学院心理生理学研究室，芜湖 241002；²皖南医学院细胞电生理研究室，芜湖 241002；³皖南医学院神经生物学研究室，芜湖 241002

摘要

创伤后应激障碍(post-traumatic stress disorder, PTSD)会增加心血管疾病患病率，而杏仁核在调控心血管功能中发挥重要作用。本研究旨在探究PTSD模型大鼠杏仁核谷氨酸受体对心血管活动的调节作用。采用电刺激与单次延长应激相结合的复合应激方法制备PTSD模型，通过分析造模前后体重变化差异以及高架十字迷宫实验进行模型检测。用荧光金(FluoroGold, FG)逆行示踪技术观察逆行标记神经元分布。用Western blot检测杏仁核谷氨酸受体含量变化。分别在PTSD大鼠中央杏仁核(the central nucleus of the amygdala, CeA)微量注射人工脑脊液、非选择性谷氨酸受体阻断剂KYN、AMPA受体阻断剂CNQX，用在体多通道同步记录技术观察注射药物后各项指标的变化。结果显示，PTSD组大鼠体重增长明显小于对照组(P < 0.01)，开放臂停留时间占比明显降低(P < 0.05)。在延髓头端腹外侧区(rostral ventrolateral medulla, RVLM)注射FG后，在CeA内观察到逆行标记神经元。PTSD组杏仁核AMPA受体含量低于对照组(P < 0.05)，CeA注射ACSF后，PTSD大鼠RVLM神经元放电频率、心率并无明显变化(P > 0.05)，而注射KYN或CNQX后，PTSD大鼠RVLM神经元放电频率、心率均加快(P < 0.05)。以上结果提示，杏仁核AMPA受体可能通过抑制性通路参与PTSD大鼠心血管活动调节。

关键词： 创伤后应激障碍; 杏仁核; 头端腹外侧区; 谷氨酸受体; 心血管功能

The impact of amygdala glutamate receptors on cardiovascular function in rats with post-traumatic stress disorder

WU Ya-Yang^1,2, CAI Kun-Yi^1,2, WU Yu-Jie^1,2, ZHENG Chao³, WANG Meng-Ya², ZHANG Huan-Huan^1,*

¹Psychophysiology Laboratory, Wannan Medical College, Wuhu 241002, China；²Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu 241002, China；³Neurobiology Laboratory, Wannan Medical College, Wuhu 241002, China

Abstract

Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.

Key words: post-traumatic stress disorder; amygdala; rostral ventrolateral medulla; glutamate receptor; cardiovascular function

收稿日期：　　录用日期：

通讯作者：张环环　　E-mail: zhanghuanhuan@wnmc.edu.cn

DOI: 10.13294/j.aps.2023.0067

引用本文：

吴亚洋, 蔡坤宜, 吴雨洁, 郑超, 汪萌芽, 张环环. 杏仁核谷氨酸受体对创伤后应激障碍模型大鼠心血管功能的作用[J]. 生理学报 2023; 75 (5): 611-622.

WU Ya-Yang, CAI Kun-Yi, WU Yu-Jie, ZHENG Chao, WANG Meng-Ya, ZHANG Huan-Huan. The impact of amygdala glutamate receptors on cardiovascular function in rats with post-traumatic stress disorder. Acta Physiol Sin 2023; 75 (5): 611-622