Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
BMC Cardiovasc Disord. 2020 Feb 5;20(1):60. doi: 10.1186/s12872-020-01363-x.
Malignant ventricular arrhythmia (VA) is the most common cause of death associated with acute myocardial infarction (MI). Recent studies have revealed direct involvement of the paraventricular nucleus (PVN) in the occurrence of VA. However, the underlying mechanisms remain incompletely understood. In this study, we investigated changes in the interleukin-6 (IL-6)-glycoprotein 130-signal transducer and activator of transcription 3 (STAT3) pathway in the PVN during acute MI and the effects of this pathway on ventricular stability.
Rats were divided into a control group, a MI group, a PVN-injected anti-IL-6 antibody group and a PVN-injected SC144 group to observe how IL-6 and its downstream glycoprotein 130-STAT3 pathway in the PVN affect ventricular stability. The left anterior descending coronary artery was ligated to induce MI. After that, an anti-IL-6 antibody and SC144 were injected into the PVNs of rats. All data are expressed as the mean ± SE and were analysed by ANOVA with a post hoc LSD test. p < 0.05 was considered to indicate statistical significance.
After MI, the concentration of the inflammatory factor IL-6 increased, and its downstream glycoprotein 130-STAT3 pathway was activated in the PVN. After injection of MI rat PVNs with the anti-IL-6 antibody or glycoprotein 130 inhibitor (SC144), glutamate levels increased and γ-aminobutyric acid (GABA) levels decreased in the PVN. Plasma norepinephrine concentrations also increased after treatment, which increased the vulnerability to VA.
In summary, IL-6 in the PVN exerts a protective effect in MI rats, and the glycoprotein 130-STAT3 pathway plays a key role in this process. We anticipate that our findings will provide new ideas for the prevention and treatment of arrhythmia after MI.
恶性室性心律失常（VA）是与急性心肌梗死（MI）相关的最常见死亡原因。最近的研究表明，旁室核（PVN）直接参与了 VA 的发生。然而，其潜在机制仍不完全清楚。在这项研究中，我们研究了急性 MI 期间 PVN 中白细胞介素-6（IL-6）-糖蛋白 130-信号转导子和转录激活子 3（STAT3）通路的变化，以及该通路对心室稳定性的影响。
将大鼠分为对照组、MI 组、PVN 注射抗 IL-6 抗体组和 PVN 注射 SC144 组，观察 IL-6 及其下游糖蛋白 130-STAT3 通路在 PVN 中如何影响心室稳定性。结扎左前降支冠状动脉诱导 MI。之后，将抗 IL-6 抗体和 SC144 注入大鼠的 PVN。所有数据均表示为均数±标准差，并采用方差分析和 LSD 事后检验进行分析。p<0.05 表示具有统计学意义。
MI 后，炎性因子 IL-6 浓度增加，PVN 中其下游糖蛋白 130-STAT3 通路被激活。在向 MI 大鼠的 PVN 注射抗 IL-6 抗体或糖蛋白 130 抑制剂（SC144）后，PVN 中的谷氨酸水平升高，γ-氨基丁酸（GABA）水平降低。治疗后血浆去甲肾上腺素浓度也升高，这增加了 VA 的易感性。
综上所述，PVN 中的 IL-6 在 MI 大鼠中发挥保护作用，糖蛋白 130-STAT3 通路在这一过程中发挥关键作用。我们预计，我们的研究结果将为 MI 后心律失常的预防和治疗提供新的思路。
