| Purpose:Atrial fibrillation(AF),one of the most common arrhythmias in clinical practice,which can result hemodynamic disorders and thromboembolism,seriously endanger people's physical and mental health.So,it is necessary to explore its pathogenesis.Studies have shown that atrial remodeling caused by cardiomyocyte apoptosis was one of the most important mechanisms for the occurrence and maintenance of AF,and reversal of atrial remodeling could prevent the occurrence of AF.Both endoplasmic reticulum stress(ERS)response and autophagy could mediate apoptosis signal transduction pathways,which could cause cardiomyocyte apoptosis and tissue damage.However,there were few studies on the relationship between AF and ERS as well as autophagy,especially the relationship with left atrial appendage(LAA)structural changes in AF patients.For this reason,our study examines the levels of ERS and autophagy related factors in plasma of patients with chronic AF to further explore their relationship with AF and provide new ideas for clinical prevention and treatment of AF.Method:1.Subject selection: According to the 2016 European AF management guidelines,63 chronic AF patients were selected in our hospital from January 2017 to January 2018.There were 37 males and 26 females,with an average age of 68.05±10.41 years.Among them,there were 27 patients with paroxysmal atrial fibrillation(PAF),15 males and 12 females,with an average age of 65.78±9.31 years.There were 18 patients with persistent atrial fibrillation(PeAF),12 males and 6 females,with an average age of 69.72±10.59 years.There were 18 patients with permanent atrial fibrillation(PmAF),10 males and 8 females,with an average age of 69.78±11.66 years.Meanwhile 15 patients with sinus rhythm(SR)group,8 males and 7 females,with an average age of 62.80±8.97 years,who had no history of arrhythmia and AF.Based on the spirit of the Declaration of Helsinki,all the patients need to get approved by Ethics Committee in hospital before examination and obtain permission from patients and their family members.Age,gender,blood pressure,laboratory examination,electrocardiogram and echocardiography were all recorded in every patient(heart,abdomen).Among them,13 PAF patients and 10 Pe AF patients underwent transesophageal echocardiography(TEE)examination.Malignant neoplasms,infectious diseases,pulmonary fibrosis,cardiac function III~IV(NYHA classification),severe liver and renal nsufficiency,ischemic cardiomyopathy,recent(within 1 month)acute myocardial infarction,cardiomyopathy,rheumatic and valvular heart disease,severely uncontrolled high blood pressure(blood pressure?160/100mmHg),endocrine diseases(aldosteronism,Cushing disease,hyperthyroidism or hypothyroidism,etc.),autoimmune diseases,recent(within 1 month)major surgical were all excluded.2.Experimental method: Every patient was collected the fasting cubital venous blood 5mL,which was centrifuged,took the supernatant and stored at-80°.The levels of glucose regulated protein 78(GRP78),CCAAT/enhancer binding protein homologous protein(CHOP)and Beclin-1 in plasma were determined by ELISA.Before TEE,patients should have completed preoperative examination,fasted for solid and liquid at least 8~12h,signed a consent form,and then took 20 m L oxybuprocaine hydrochloride gel for local anesthesia of the pharyngeal mucosa.Patients took a supine position on the examination bed,were connected the electrocardiogram and then were sent the probe into the esophagus through the mouthpiece.Then we took the clear two-dimensional images and blood flow velocity spectrum images at the left atrial appendage opening around 45°and 90°.The left atrial appendage width(LAAW)and left atrial appendage length(LAAL)were measured.In the LAA blood flow spectrum under AF rhythm,the maximum positive wave was recorded as left atrial appendage emptying velocity(LAA-EV),and the maximum negative wave was recorded as left atrial appendage filling velocity(LAA-FV).3.Statistical method: all the data was analyzed by the statistical processing of SPSS 21.0.Measurement data was expressed as mean±standard deviation(`X±S).Enumeration data was used ?2 test.Single factor t test was used for comparison between groups and ANOVA was used for intragroup comparisons.Linear correlation analysis was used for correlation analysis.P<0.05 was considered statistically significant.Result:1.The levels of plasma GRP78,CHOP and Beclin-1 in AF group were higher than those in SR group,the difference between the two groups was statistically significant(P<0.05).2.The levels of plasma GRP78,CHOP and Beclin-1 in PeAF patients were higher than those in PAF patients,the difference between the two groups was statistically significant(P<0.05).The levels of plasma GRP78,CHOP and Beclin-1 in PmAF patients were higher than those in PAF patients,the difference between the two groups was statistically significant(P<0.05).The levels of plasma GRP78,CHOP and Beclin-1 in PeAF patients were slightly higher than those in PmAF patients,but the difference between the two groups was no statistically significant(P>0.05).3.Among the patients who were measured LAA,LAAW and LAAL in PeAF patients were higher than those in PAF patients,and LAA-EV and LAA-FV were lower than those in PAF patients,the difference between the two groups was statistically significant(P<0.05).In addition,the levels of plasma GRP78,CHOP and Beclin-1 in PeAF patients were also higher than those in PAF patients,the difference between the two groups was statistically significant(P<0.05).4.The levels of plasma GRP78 were positively correlated with LAAW and LAAL,the difference was statistically significant(r=0.571,P<0.05;r=0.592,P<0.05),and negatively correlated with LAA-EV and LAA-FV,the difference was statistically significant(r=-0.599,P<0.05;r=-0.48,P<0.05).The levels of plasma CHOP were positively correlated with LAAW and LAAL,the difference was statistically significant(r=0.498,P<0.05;r=0.439,P<0.05),and negatively correlated with LAA-EV and LAA-FV,the difference was statistically significant(r=-0.421,P<0.05;r=-0.438,P<0.05).The levels of plasma Beclin-1 were positively correlated with LAAW and LAAL,the difference was statistically significant(r=0.419,P<0.05;r=0.5,P<0.05),and negatively correlated with LAA-EV and LAA-FV,the difference was statistically significant(r=-0.487,P<0.05;r=-0.526,P<0.05).Conclusion:1.ERS and autophagy are closely related to the occurrence,development and maintenance of chronic AF.2.LAAW,LAAL,LAA-EV and LAA-FV are involved in the pathological process of AF.3.There is a certain relationship between ERS as well as autophagy and LAA structural reconstruction.4.ERS and autophagy may have certain predictive effects on the progression of AF. |
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