Effect of renal denervation on atrial neural and structural remodeling in rats with obesity-related atrial fibrillation and its mechanism
AIM:To investigate the role of renal denervation(RDN)in treatment of obesity-related atrial fi-brillation(AF)in rats.METHODS:A high-fat diet AF-susceptible rat model was constructed.The rats in control group was fed with a standard diet,while those in RDN group was subjected to RDN via surgical and chemical ablation.The re-nal tyrosine hydroxylase expression level was detected by Western blot.An in vivo electrophysiological instrument was used to detect the cardiac electrophysiological parameters of rats,including atrial effective refractory period(AERP),AF induction rate,and AF duration.Alterations in cardiac structure and function of the rats were assessed using echocar-diography.PowerLab bioinformatics acquisition system was used to analyze alterations in the tension of the rat cardiac au-tonomic nervous system.Transmission electron microscopy was used to further observe structural changes in the rat atrial mitochondria.The protein levels of mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR)were detected by Western blot.Masson staining and HE staining were used to detect the extent of structural changes in the left atrium.RESULTS:(1)Compared with standard diet group,the AF induction rate and duration of the rats fed with a high-fat diet were significantly increased;however,the AERP significantly decreased.RDN reduced the increases in AF induction rate and duration in the rats fed with a high-fat diet,and even restored the AERP.(2)Cardiac low frequency significantly increased whereas cardiac high frequency decreased in heart autonomic nerves of the rats fed with a high-fat diet.After RDN,low frequency was significantly restored,suggesting that RDN could reverse the cardiac autonomic ner-vous system disorder induced by a high-fat diet.(3)Ultrasound results showed that compared with standard diet group,the left atrial diameter and left ventricular end-systolic diameter(LVESD)of the rats fed with high-fat diet were increased,whereas the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were decreased.Af-ter RDN,the LVEF and LVFS of high-fat diet-fed rats increased,whereas the LVESD decreased.Ultrasound results showed that RDN could attenuate the cardiac functional and structural damage induced by a high-fat diet.Masson and HE staining results showed that compared with standard diet group,atrial fibrosis and atrial cardiomyocyte hypertrophy in-creased in high-fat diet-fed rats,while atrial fibrosis was significantly attenuated after RDN.(4)Transmission electron mi-croscopy showed that the functional structure of atrial mitochondria in high-fat diet-fed rats was damaged,with disordered arrangement and increased number of vacuoles.Western blot results showed that mTOR and p-mTOR protein levels in-creased in the left atrium of high-fat diet-fed rats.Mitochondrial autophagy and structural damage were attenuated after RDN.CONCLUSION:Renal denervation may reduce high-fat diet-induced AF susceptibility via alleviating autonomic nervous system disorders and cardiac structural and functional remodeling.
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