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

Abstract

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 Coptidis Rhizoma and Rhizoma Pinelliae Preparata, 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 in vivo 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.

Acupuncture for neuropathic pain: focusing on the sympathetic nerve system

“…The intact axons left in the degenerating stump transport NGF from the zones of Wallerian degeneration in the nerve stump to the DRG, where it induces sympathetic sprouting [42,47] . A similar study found that the tyrosine kinase-A (TrkA) mediated the uptake of NGF into spared axons within the degenerating distal stump [48] . However, sympathetic axons in Wallerian degeneration-deficient Wld s mice, sprout after SNL to the same extent as in control wild-type mice [34] .…”

The application and mechanism of Chinese medicine in the upstream treatment of atrial fibrillation

“…The nerve growth factor (NGF)/tyrosine kinase receptor A (TrKA)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is an important target for reducing sympathetic remodeling after myocardial infarction ( 34 , 35 ). Some scholars found that Lianxia Formula Granule could inhibit the expression of key proteins and mRNAs of NGF/TrKA/PI3K/AKT signaling pathway and suppress catecholamine levels, thus attenuating sympathetic remodeling and reducing arrhythmia susceptibility ( 36 ), as presented in Table 5 . Current research on the effects of TCM on the autonomic nervous system of AF is relatively limited, and more exploration is needed.…”