The stellate ganglia play an important role in cardiac remodeling after myocardial infarction (MI). This study aimed to investigate whether adiponectin (APN), an adipokine mainly secreted by adipose tissue, could modulate the left stellate ganglion (LSG) and exert cardioprotective effects through the sympathetic nervous system (SNS) in a canine model of MI. APN microinjection and APN overexpression with recombinant adeno-associated virus vector in the LSG were performed in acute and chronic MI models, respectively. The results showed that acute APN microinjection decreased LSG function and neural activity, and suppressed ischemia-induced ventricular arrhythmia. Chronic MI led to a decrease in the effective refractory period and action potential duration at 90% and deterioration in echocardiography performance, all of which was blunted by APN overexpression. Moreover, APN gene transfer resulted in favorable heart rate variability alteration, and decreased cardiac SNS activity, serum noradrenaline and neuropeptide Y, which were augmented after MI. APN overexpression also decreased the expression of nerve growth factor and growth associated protein 43 in the LSG and peri-infarct myocardium, respectively. Furthermore, RNA sequencing of LSG indicated that 4-week MI up-regulated the mRNA levels of macrophage/microglia activation marker Iba1, chemokine ligands (CXCL10, CCL20), chemokine receptor CCR5 and pro-inflammatory cytokine IL6, and downregulated IL1RN and IL10 mRNA, which were reversed by APN overexpression. Our results reveal that APN inhibits cardiac sympathetic remodeling and mitigates cardiac remodeling after MI. APN-mediated gene therapy may provide a potential therapeutic strategy for the treatment of MI.

星状神经节在心肌梗死 (MI) 后的心脏重塑中起重要作用。本研究旨在研究脂联素 (APN) 是一种主要由脂肪组织分泌的脂肪因子，它是否可以调节左侧星状神经节 (LSG) 并通过交感神经系统 (SNS) 在心肌梗死犬模型中发挥心脏保护作用。APN 显微注射和重组腺相关病毒载体在 LSG 中的 APN 过表达分别在急性和慢性 MI 模型中进行。结果表明，急性 APN 显微注射降低了 LSG 功能和神经活动，并抑制了缺血引起的室性心律失常。慢性 MI 导致有效不应期和动作电位持续时间减少 90%，超声心动图性能恶化，所有这些都因 APN 过度表达而减弱。此外，APN 基因转移导致有利的心率变异性改变，并降低心脏 SNS 活性、血清去甲肾上腺素和神经肽 Y，这些在 MI 后增加。APN 过表达还分别降低了 LSG 和梗塞周围心肌中神经生长因子和生长相关蛋白 43 的表达。此外，LSG 的 RNA 测序表明，4 周 MI 上调巨噬细胞/小胶质细胞激活标志物 Iba1、趋化因子配体（CXCL10、CCL20）、趋化因子受体 CCR5 和促炎细胞因子 IL6 的 mRNA 水平，并下调 IL1RN 和 IL10 mRNA ，这被 APN 过度表达所逆转。我们的结果表明 APN 抑制心脏交感神经重塑并减轻 MI 后的心脏重塑。