LianXia Formula Granule Attenuates Cardiac Sympathetic Remodeling in Rats with Myocardial Infarction via the NGF/TrKA/PI3K/AKT Signaling Pathway.

Sympathetic remodeling may cause severe arrhythmia after myocardial infarction (MI). Thus, targeting this process may be an effective strategy for clinical prevention of arrhythmias. LianXia Formula Granule (LXFG) can effectively improve the symptoms of patients with arrhythmia after MI, and modern pharmacological studies have shown that and , the components of LXFG, have antiarrhythmia effects. Here, we investigated whether LXFG can mitigate sympathetic remodeling and suppress arrhythmia and then elucidated its underlying mechanism of action in rats after MI. Sprague-Dawley (SD) rats that had undergone a myocardial infarction model were randomly divided into 6 groups, namely, sham, model, metoprolol, and LXFG groups, with high, medium, and low dosages. We exposed the animals to 30 days of treatment and then evaluated incidence of arrhythmia and arrhythmia scores using programmed electrical stimulation. Moreover, we determined plasma catecholamines contents via enzyme-linked immunosorbent assay and detected expression of tyrosine hydroxylase (TH) at infarcted border zones via western blot, real-time PCR, and immunohistochemical analyses to assess sympathetic remodeling. Finally, we measured key molecules involved in the NGF/TrKA/PI3K/AKT pathways via western blot and real-time PCR. Compared with the model group, treatment with high dose of LXFG suppressed arrhythmia incidence and arrhythmia scores. In addition, all the LXFG groups significantly decreased protein and mRNA levels of TH, improved the average optical density of TH-positive nerve fibers, and reduced the levels of plasma catecholamines relative to the model group. Meanwhile, expression analysis revealed that key molecules in the NGF/TrKA/PI3K/AKT pathways were downregulated in the LXFG group when compared with model group. Overall, these findings indicate that LXFG suppresses arrhythmia and attenuates sympathetic remodeling in rats after MI. The mechanism is probably regulated by suppression of the NGF/TrKA/PI3K/AKT signaling pathway.