| Background: Previous studies have revealed a high incidence of atrial fibrillation (AF) following myocardial infarction (MI). Structural remodeling and electrical remodeling in the atrium are the primary mechanisms observed to underlie this AF; however, cardiac neural remodeling has also been noted with increasing frequency. Cardiac neural remodeling, along with structural and electrical remodeling, is currently believed to play an important role in the initiation and maintenance of AF. MI induces cardiac neural remodeling; moreover, post-MI neural remodeling is not limited to the infarcted myocardium but also involves the non-infarcted atrial myocardium and even nerve tissues outside the myocardium. In a canine model of MI, Zhou et al. demonstrated an increased expression of nerve growth factor (NGF) and growth-associated protein-43 (GAP43) in infarcted cardiac tissue and showed that these proteins were the principal inducers of nerve sprouting in non-infarcted areas. They inferred that the increased levels of NGF in the left stellate ganglion (LSG) most likely resulted from the retrograde axonal transport of NGF released from the myocardium after MI because there was no change in NGF mRNA levels in the LSG. Other studies have also found that MI triggers nerve sprouting in the stellate ganglia (SG). Neural remodeling of the SG can affect the neural remodeling of the ventricles and induce ventricular arrhythmias after MI. However, the effects of SG neural remodeling on the neural remodeling of the atrium and atrial arrhythmias remain incompletely understood. Moreover, the relationship between neural remodeling in the LSG and in the left atrium (LA) is not well understood, In the present study, we investigated the mechanism by which the LSG mediates sympathetic neural remodeling of the LA in rats after an MI. The neural remodeling of the atrium plays an important role in the initiation of atrial fibrillation (AF) after myocardial infarction (MI); however, the effects of the left stellate ganglion (LSG) on the neural remodeling of the atrium remain incompletely understood. Thus, this study investigated the mechanism by which the LSG mediates sympathetic neural remodeling of the left atrium (LA) in rats after MI.Methods: A total of 80 male Wistar rats were randomly divided into 3 groups:the sham operation group (S group), MI+rosuvastatin intervention group (R group), and the MI group (I group). The AMI model was established using the anterior descending coronary artery ligation. The levels of nerve growth factor (NGF) and growth associated protein 43 (GAP43) positive substances in the LA and left stellate ganglion (LSG) were analyzed using immunohistochemistry to reflect the distribution and density of nerve fibers. The protein expression levels of NGF and GAP43 were detected using western blotting, and the mRNA expression levels of NGF and GAP43 in the LA and LSG tissues of rats in each group were detected using RT-PCR.Results: Compared with the S group, the AOD values of NGF positive substances in LSG of the R and I groups both significantly increased (0.062±0.027 & 0.081±0.052 vs.0.005±0.007, P＜0.01). Compared with the I group, the AOD values of NGF (0.062±0.027 vs.0.081 ±0.052, P＜0.01) positive substances in LSG in the R group decreased significantly (P＜0.01).Compared with the S group, the AOD values of GAP43 positive substances in LSG in the R and I groups both significantly increased (0.046±0.038 & 0.057±0.027 vs.0.027±0.002, P＜0.01). Compared with the I group, the AOD values of GAP43 positive substances in LSG in the R group decreased significantly (0.046±0.038 vs.0.057±0.027, P＜0.01). Compared with the S group, The AOD values of NGF positive substances in LA in the R and I groups both significantly increased (0.01±0.005 & 0.017±0.015 vs. 0.003±0.003, P＜0.01). Compared with the S group, the AOD values of GAP43 positive substances in LA in the R and I groups significantly increased (0.045±0.024 & 0.064±0.041 vs. 0.012±0.011, P＜0.01). Compared with the I group, the AOD value of GAP43 positive substances in the R group significantly decreased (0.045±0.024 vs.0.064±0.041, P＜0.01). Compared with the I group, the AOD values of NGF positive substances in the R group significantly decreased (0.01±0.005 vs.0.017±0.015, P<0.01).The protein expression levels of GAP43 and NGF in the LSG and LA in the I and R groups were significantly higher than in the S group (all P＜0.01).Compared with the I group, protein expression levels of GAP43 in the LSG and LA in the R group decreased significantly (P＜0.01), while the differences in the protein expression levels of NGF did not reach statistical significance. The expression levels of GAP43 mRNA in LSG in the I and R groups were significantly higher than in the S group (both P＜0.01), the level in the R group was significantly lower than in the I group (P＜0.01), and the expression levels of NGF mRNA among these groups did not exhibit significant differences. The expression levels of NGF mRNA in LA in the I and R groups were significantly higher than in the S group (both P＜0.01), the level in the R group was lower than in the I group (P＜0.01), and the expression levels of GAP43 mRNA among these groups did not exhibit significant differences.Conclusions:1.The increased levels of NGF and GAP43 proteins can induce sympathetic nerve hyperinnervation in the LSG and the LA after MI.2.The increased GAP43 proteins in the LA, which may have been transported from the LSG, accelerated LA sympathetic neural remodeling in rats.3.Rosuvastatin could effectively improve the sympathetic neural remodeling of LA in MI rats. The mechanism might be associated with the direct inhibition of expression and protein synthesis of GAP43 in the LSG and LA. |
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