目的了解酪氨酸羟化酶(TH)与生长相关蛋白43(GAP43)基因在心房颤动(房颤)形成与恢复过程中的表达变化及其意义。方法山羊24只,随机分为窦性心律组(窦律组)、房颤组、复律3个月组与复律6个月组(各6只)。开胸后于左心耳与左心房前壁连接处植入起搏电极导线,以(400±10)次/min连续起搏3个月,诱导房颤。复律组采用电复律法恢复窦性心律3~6个月。每周记录山羊体表心电图,分别采用Western blot与免疫组化方法检测TH与GAP43基因在窦律组、房颤组、复律3个月组与复律6个月组的蛋白水平变化。结果免疫组化检测结果显示房颤组左心房游离壁TH与GAP43基因蛋白水平较窦律组显著增高,差异有统计学意义[(22.50±16.47)个/mm^2vs(3.24±1.55)个/mm^2,(35.75±20.31)个/mm^2vs(4.83±3.97)个/mm^2,P〈0.01];复律3个月组,左心房游离壁TH与GAP43基因蛋白水平[(17.42±10.54)个/mm^2,(20.38±22.96)个/mm^2]较房颤组明显降低(P〈0.05);复律6个月组,左心房游离壁TH与GAP43基因蛋白水平[(6.73±2.94)个/mm^2,(8.58±5.07)个/mm^2]较房颤组也明显降低(P〈0.01)。右心房游离壁TH与GAP43基因蛋白水平在房颤组、复律3个月组与复律6个月组变化趋势与左心房游离壁相似。Western blot检测结果与免疫组化结果一致。结论TH与GAP43基因表达变化在房颤形成与恢复过程中起着重要作用,可能是房颤治疗的潜在靶点。
Objective To explore the expression of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) gene in the process of atrial fibrillation(AF) formation and resumption in a goat model. Methods Twenty-four goats were randomly assigned into sinus rhythm group (n = 6), AF group (n = 6), post AF 3-month group ( n = 6), and post AF 6-month group ( n = 6). Except sinus rhythm group goats, all other goats received continuous pacing at the junction of the left atrial appendage and the front wall of the left atrium with (400 ±10) times/min for 3 months. Direct-current cardioversion was used to restore sinus rhythm. Surface electrocardiog-rams ECGs were recorded weekly. Western blot and immunohistochemistry were used to investigate the protein expression of the tissue from left and right atrial free wall. Results hnmunohistochemistry showed that the protein expression of TH and GAP43 in the left free wall increased significantly in AF group ( (22.50 ± 16.47 ) /mm^2 and ( 35.75 ± 20. 31 )/mm^2 ) compared with control one [ ( 3.24 ± 1.55 )/mm^2 and (4. 83 ± 3.97 )/mm^2 , P 〈 0. 01 respectively) , and these proteins reduced remarkably in post AF 3-month group ( 17.42 ± 10. 54) /mm^2 and ( 20. 38 ± 22. 96 )/mm^2 ) and post AF 6-month one [ (6. 73 ± 2. 94)/mm^2, ( 8.58±5.07)/mm^2 ,P 〈0. 013. The fluetuation trend of the protein level of TH and GAP43 determined by wesstern blot was similar with immunohistoehemistry. Conclusion TH and GAP43 expression play very important role in the process of AF formation and resmnption in goats model ,which may be a potential target for clinical treatment.