Cheng Lijun, Yu Lin, Zhan Xiaoping, Tse Gary, Liu Tong, Fu Huaying, Li Guangping
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China.
J Cardiovasc Dev Dis. 2023 Feb 6;10(2):71. doi: 10.3390/jcdd10020071.
The superior cervical ganglion (SCG) plays a key role in cardiovascular diseases. The aim of this study was to determine the changes in the ion channel characteristics of the SCG following myocardial infarction (MI) and the role of pretreatment with the P2Y12 receptor antagonist ticagrelor (TIC).
A total of 18 male rabbits were randomly divided into a control group, MI group, and P2Y12 receptor antagonist (TIC) group (abbreviated as the TIC group). Rabbit MI was performed via two abdominal subcutaneous injections of 150 mg·kg·d of isoproterenol (ISO) with an interval of 24 h. TIC pretreatment at 20 mg·kg·d was administered via gavage for two consecutive days. The cardiac function of each group was evaluated with echocardiography. ADP receptor P2Y12 expressions in SCGs were determined using RT-PCR and immunofluorescence staining. Ion channel characteristics of SCG neurons were measured using a whole-cell patch clamp. Intracellular calcium concentrations for SCG neurons were measured using confocal microscopy.
Cardiac function was reduced in the rabbits of the MI group, the sympathetic nerve activity of SCGs was increased, and the current amplitude of the neuron ion channel was increased. MI led to alterations in the activation and inactivation characteristics of channels accompanied by increased expression of P2Y12 in SCGs. Most of these abnormalities were prevented by TIC pretreatment in the TIC group.
TIC pretreatment could attenuate the increase in P2Y12 expression in SCGs and the changes to the ion channel characteristics of SCG neurons after MI. This may be the mechanism underlying the cardiac protective effects of TIC.
颈上神经节（SCG）在心血管疾病中起关键作用。本研究旨在确定心肌梗死（MI）后SCG离子通道特性的变化以及P2Y12受体拮抗剂替格瑞洛（TIC）预处理的作用。
将18只雄性兔子随机分为对照组、MI组和P2Y12受体拮抗剂（TIC）组（简称为TIC组）。通过两次腹部皮下注射150mg·kg·d的异丙肾上腺素（ISO），间隔24小时，诱导兔子发生MI。连续两天通过灌胃给予20mg·kg·d的TIC进行预处理。用超声心动图评估每组的心脏功能。使用RT-PCR和免疫荧光染色测定SCG中ADP受体P2Y12的表达。使用全细胞膜片钳测量SCG神经元的离子通道特性。使用共聚焦显微镜测量SCG神经元的细胞内钙浓度。
MI组兔子的心脏功能降低，SCG的交感神经活性增加，神经元离子通道的电流幅度增加。MI导致离子通道的激活和失活特性发生改变，同时SCG中P2Y12的表达增加。TIC组通过TIC预处理可预防这些异常中的大多数。
TIC预处理可减轻MI后SCG中P2Y12表达的增加以及SCG神经元离子通道特性的变化。这可能是TIC心脏保护作用的潜在机制。
