The Research Of Pathogenesis About Atrial Fibrillation Cause Of Hyperthyroidism Associated With Atrial Sympathetic Nerve

Objective:To establish an animal model of susceptibility to hyperthyroidism-induced atrial fibrillation to further study the role and pathogenesis of atrial sympathetic nerve in the occurrence and development of hyperthyroidism-induced atrial fibrillation.At the animal level,it provides further theoretical support for the sympathetic nervous system to participate in the occurrence of hyperthyroidism-induced atrial fibrillation,and provides a new treatment concept and direction for hyperthyroidism patients with atrial fibrillation.Methods:(1)Establishment of rabbit model of hyperthyroidism-induced atrial fibrillation:the healthy 50 adult Japanese white rabbits were divided into three groups by randomization:control group of 10(intraperitoneal injection of equal dose of normal saline for 4 months),20 in 2-month administration group(thyroid hormone solution 50ug/Kg intraperitoneally every day for 2 months),20 in 4-month administration group(intraperitoneal injection of 50ug/Kg of thyroid hormone solution every day for 4 months).Record the rabbit’s body weight,heart rate and ECG before the experiment.(2)Electrophysiological test of left atrium:Atrial effective refractory period(AERP)was measured in three groups at 200 ms and 150 ms after stimulation in 2 months and 4 months respectively,and record induced rate of atrial fibrillation.(3)At the end of the experiment,animal models were collected ear vein blood and left atrial tissue material collection.(4)Serum norepinephrine(NE)was detected by enzyme-linked immunosorbent assay(ELISA).(5)The expression of Tyrosine Hydroxylase(TH)and Growth Associated Proteins-43(GAP-43)in the left atrial tissue of rabbits was detected by immunohistochemistry and the positive nerve fiber density was calculated.(6)Western blot analysis of TH and GAP-43 expression and analysis of their relative protein expression.(7)Quantitative real-time PCR:Total RNA from three groups of rabbit left atrial tissue was extracted and reverse transcribed.The relative mRNA expression of TH and GAP-43 in each group was detected.Results:(1)Animal experiment basic index results:There was no statistical difference in body weight and heart rate between the three groups before the start of the experiment;after the end of the experiment,compared with the control group,in the 2 months group and 4 months group,the body weight decreased and the heart rate increased,the difference was statistically significant(P<0.05);The body weight of the 4 months group was even lower than that of the 2 months group,and the difference was statistically significant(P<0.05).However,there was no statistical difference in the results of heart rate between the 2 groups.(2)Left atrial electrophysiological test results:Compared with the control group:the left atrial effective refractory period was shortened in the 2 months group and the 4 months group,and the 4 months group was further shortened compared with the 2 months group.And the difference was statistically significant(P<0.05).(3)Atrial fibrillation induced results:Compared with the control group and the 2 months group,the induction rate of atrial fibrillation is increased in the 4 months group,and the difference was statistically significant(P<0.05);There was no statistical difference in the results of atrial fibrillation induced rate of between the 2 months group and the control group.(4)ELISA test NE results:compared with the control group:serum norepinephrine levels increased in the 2 months group and 4 months group(P<0.05);There was no statistical difference between the 4 months group and the 2 months group.(5)Western blot results showed that ①the expression of TH protein in the 4 months group and the 2 months group was higher than the control group(P<0.05);compared the 4 months group and 2 months group,the difference was not statistically significant.②The expression of GAP-43 protein in the 2 months group and 4 months group was higher than the control group(P<0.05);The expression of GAP-43 protein in the 4 months group was significantly higher than the 2 months group(P<0.05).(6)Quantitative real-time PCR results:①The mRNA expression of TH in the 2 months group and the 4 months group were significantly higher than the control group(P<0.05);There was no statistical difference in TH mRNA expression between the 4 months group and 2 months group.②The mRNA expression levels of GAP-43 in the 2 months group and the 4 months group were higher than the control group(P<0.05);The mRNA expression level of GAP-43 was higher in the 4 months group than in the 2 months group.The difference was statistically significant(P<0.05).(7)Results of immunohistochemistry:①Compared with the control group,the average density of TH-positive nerve fibers in the left atrium tissue of the 2 months group and the 4 months group were significantly higher.The difference was statistically significant(P<0.05);No statistical difference between the 4 months group and 2 months group.②Compared with the control group,the mean value of GAP-43-positive nerve fiber density increased in the 2 months group and the 4 months group,the difference was statistically significant(P<0.05);The nerve fiber density of the 4 months group was higher than the 2 months group,and the difference was statistically significant(P<0.05).Conclusions:One of the mechanisms of sustained high thyroid hormone-induced atrial fibrillation may be through the role in the sympathetic nervous system,so that the atrial sympathetic nerve is over-activated,causing left atrial sympathetic nervous remodeling,resulting in shortening of the left atrium effective refractory period,making Atrial fibrillation is easily induced.