• 四川大學華西醫(yī)院心血管內(nèi)科（成都，610041）;

心房顫動（房顫）是臨床上常見的心律失常，具有很高的致殘率及致死率。房顫及其并發(fā)癥對人類健康造成了巨大的危害，且發(fā)病率及患病率逐年升高。了解房顫的發(fā)病機制，有助于房顫的預防及治療。近年來，對房顫的發(fā)病機制主要集中在電重構、結構重構、炎癥及基因遺傳等方面，現(xiàn)將其研究進展作一闡述。

引用本文： 何森,王斯,陳曉平. 心房顫動發(fā)病機制的研究進展. 華西醫(yī)學, 2012, 27(5): 794-797. doi: 復制

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1. 　Wolf PA, Dawber TR, Thomas HE Jr, et al. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study[J]. Neurology, 1978, 28(10): 973-977.
2. 　Seiler J, Stevenson WG. Atrial fibrillation in congestive heart failure[J]. Cardiol Rev, 2010, 18(1): 38-50.
3. 　Ott A, Breteler MM, de Bruyne MC, et al. Atrial fibrillation and dementia in a population-based study. The Rotterdam Study[J]. Stroke, 1997, 28(2): 316-321.
4. 　Hu D, Sun Y. Epidemiology, risk factors for stroke, and management of atrial fibrillation in China[J]. J Am Coll Cardiol, 2008, 52(10): 865-868.
5. 　Mattle HP. Long-term outcome after stroke due to atrial fibrillation[J]. Cerebrovasc Dis, 2003, 16(Suppl 1): 3-8.
6. 　Mattle HP, Schwerzmann M, Seiler C. Atrial fibrillation and stroke[J]. Ther Umsch, 2003, 60(9): 527-534.
7. 　Dobrev D. Electrical remodeling in atrial fibrillation[J]. Herz, 2006, 31(2): 108-112.
8. 　Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats[J]. Circulation, 1995, 92(7): 1954-1968.
9. 　Brundel BJ, Van Gelder IC, Henning RH, et al. Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels[J]. J Am Coll Cardiol, 2001, 37(3): 926-932.
10. 　Dobrev D, Wettwer E, Kortner A, et al. Human inward rectifier Potassium channels in chronic and postoperative atrial fibrillation[J]. Cardiovasc Res, 2002, 54(2): 397-404.
11. 　Bosch RF, Scherer CR, Rüb N, et al. Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces I (Ca,L) and I (to) in rapid atrial pacing in rabbits[J]. J Am Coll Cardiol, 2003, 41(5): 858-869.
12. 　Yue L, Feng J, Gaspo R, et al. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation[J]. Circ Res, 1997, 81(4): 512-525.
13. 　Gaborit N, Steenman M, Lamirault G, et al. Human atrial ion channel and transporter subunit gene-expression remodeling associated with valvular heart disease and atrial fibrillation[J]. Circulation, 2005, 112(4): 471-481.
14. 　Nattel S. New ideas about atrial fibrillation 50 years on[J]. Nature, 2002, 415(6868): 219-226.
15. 　Allessie M, Ausma J, Electrical SU. Contractile and structural remodeling during atrial fibrillation[J]. Cardiovasc Res, 2002, 54(2): 230-246.
16. 　Eckstein J, Verheule S, de Groot NM, et al. Mechanisms of perpetuation of atrial fibrillation in chronically dilated atria[J]. Prog Biophys Mol Biol, 2008, 97(2-3): 435-451.
17. 　吳衛(wèi), 柯丹, 許春萱, 等. Ⅰ型膠原和白細胞介素-1β在心房顫動患者心房中的表達[J]. 中華內(nèi)科雜志, 2006, 45(10): 807-810.
18. 　Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis[J]. N Engl J Med, 1994, 331(19): 1286-1292.
19. 　Tomita H, Egashira K, Ohara Y, et al. Early induction of transforming growth factor-beta via angiotensin Ⅱ type 1 receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis in rats[J]. Hypertension, 1998, 32(2): 273-279.
20. 　Verheule S, Sato T, Everett T 4th, et al. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1[J]. Circ Res, 2004, 94(11): 1458-1465.
21. 　Darbar D, Motsinger AA, Ritchie MD, et al. Polymorphism modulates symptomatic response to antiarrhythmic drug therapy in patients with lone atrial fibrillation[J]. Heart Rhythm, 2007, 4(6): 743-749.
22. 　Boldt A, Wetzel U, Weigl J, et al. Expression of angiotensin Ⅱreceptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease[J]. J Am Coll Cardiol, 2003, 42(10): 1785-1792.
23. 　Psychari SN, Apostolou TS, Sinos L, et al. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation[J]. Am J Cardiol, 2005, 95(6): 764-767.
24. 　Sawaya SE, Rajawat YS, Rami TG, et al. Downregulation of connexin40 and increased prevalence of atrial arrhythmias in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor[J]. Am J Physiol Heart Circ Physiol, 2007, 292(3): H1561-H1567.
25. 　Marín F, Corral J, Roldán V, et al. FactorⅩ Val34Leu polymorphism modulates the prothrombotic and inflammatory state associated with atrial fibrillation[J]. J Mol Cell Cardiol, 2004, 37(3): 699-704.
26. 　Aviles RJ, Martin DO, Apperson-Hansen C. Inflammation as a risk factor for atrial fibrillation[J]. Circulation, 2004, 13(3): 64.
27. 　Dernellis J, Panaretou M. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation[J]. Eur Heart J, 2004, 25(13): 1100-1107.
28. 　Santangeli P, Ferrante G, Pelargonio G, et al. Usefulness of statins in preventing atrial fibrillation in patients with permanent pacemaker: a systematic review[J]. Europace, 2010, 12(5): 649-654.
29. 　Shiroshita-Takeshita A, Schram G, Lavoie J, et al. Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodeling in dogs[J]. Circulation, 2004, 110(16): 2313-2319.
30. 　Armaganijan L, Eikelboom J, Healey JS, et al. New pharmacotherapy for stroke prevention in atrial fibrillation: Update 2010[J]. Adv Ther, 2009, 26(12): 1058-1071.
31. 　Tops LF, Schalij MJ, Bax JJ. Imaging and atrial fibrillation: the role of multimodality imaging in patient evaluation and management of atrial fibrillation[J]. Eur Heart J, 2010, 31(5): 542-551.
32. 　Nademanee K, Lockwood E, Oketani N, et al. Catheter ablation of atrial fibrillation guided by complex fractionated atrial electrogram mapping of atrial fibrillation substrate[J]. J Cardiol, 2010, 55(1): 1-12.
33. 　殷躍輝, 劉增長, 吳近近, 等. 胺碘酮與氯沙坦、培哚普利聯(lián)合治療陣發(fā)性心房顫動的前瞻、隨機開發(fā)研究[J]. 中華心血管病雜志, 2006, 34(4): 299-301.
34. 　Doughty MJ, Jonuscheit S. The orbscan acoustic (correction) factor for central corneal thickness measures of normal human corneas[J]. Eye Contact Lens, 2010, 36(2): 106-115.
35. 　Tsai CT, Lai LP, Lin JL, et al. Renin-angiotensin system gene polymorphisms and atrial fibrillation[J]. Circulation, 2004, 109(13): 1640-1646.
36. 　Firouzi M, Ramanna H, Kok B, et al. Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation[J]. Circ Res, 2004, 95(4): e29-e33.
37. 　Schreieck J, Dostal S, von Beckerath N, et al. C825T polymorphism of the G-protein beta3 subunit gene and atrial fibrillation: association of the TT genotype with a reduced risk for atrial fibrillation[J]. Am Heart J, 2004, 148(3): 545-550.
  1. 1. 　Wolf PA, Dawber TR, Thomas HE Jr, et al. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study[J]. Neurology, 1978, 28(10): 973-977.
  2. 2. 　Seiler J, Stevenson WG. Atrial fibrillation in congestive heart failure[J]. Cardiol Rev, 2010, 18(1): 38-50.
  3. 3. 　Ott A, Breteler MM, de Bruyne MC, et al. Atrial fibrillation and dementia in a population-based study. The Rotterdam Study[J]. Stroke, 1997, 28(2): 316-321.
  4. 4. 　Hu D, Sun Y. Epidemiology, risk factors for stroke, and management of atrial fibrillation in China[J]. J Am Coll Cardiol, 2008, 52(10): 865-868.
  5. 5. 　Mattle HP. Long-term outcome after stroke due to atrial fibrillation[J]. Cerebrovasc Dis, 2003, 16(Suppl 1): 3-8.
  6. 6. 　Mattle HP, Schwerzmann M, Seiler C. Atrial fibrillation and stroke[J]. Ther Umsch, 2003, 60(9): 527-534.
  7. 7. 　Dobrev D. Electrical remodeling in atrial fibrillation[J]. Herz, 2006, 31(2): 108-112.
  8. 8. 　Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats[J]. Circulation, 1995, 92(7): 1954-1968.
  9. 9. 　Brundel BJ, Van Gelder IC, Henning RH, et al. Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels[J]. J Am Coll Cardiol, 2001, 37(3): 926-932.
  10. 10. 　Dobrev D, Wettwer E, Kortner A, et al. Human inward rectifier Potassium channels in chronic and postoperative atrial fibrillation[J]. Cardiovasc Res, 2002, 54(2): 397-404.
  11. 11. 　Bosch RF, Scherer CR, Rüb N, et al. Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces I (Ca,L) and I (to) in rapid atrial pacing in rabbits[J]. J Am Coll Cardiol, 2003, 41(5): 858-869.
  12. 12. 　Yue L, Feng J, Gaspo R, et al. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation[J]. Circ Res, 1997, 81(4): 512-525.
  13. 13. 　Gaborit N, Steenman M, Lamirault G, et al. Human atrial ion channel and transporter subunit gene-expression remodeling associated with valvular heart disease and atrial fibrillation[J]. Circulation, 2005, 112(4): 471-481.
  14. 14. 　Nattel S. New ideas about atrial fibrillation 50 years on[J]. Nature, 2002, 415(6868): 219-226.
  15. 15. 　Allessie M, Ausma J, Electrical SU. Contractile and structural remodeling during atrial fibrillation[J]. Cardiovasc Res, 2002, 54(2): 230-246.
  16. 16. 　Eckstein J, Verheule S, de Groot NM, et al. Mechanisms of perpetuation of atrial fibrillation in chronically dilated atria[J]. Prog Biophys Mol Biol, 2008, 97(2-3): 435-451.
  17. 17. 　吳衛(wèi), 柯丹, 許春萱, 等. Ⅰ型膠原和白細胞介素-1β在心房顫動患者心房中的表達[J]. 中華內(nèi)科雜志, 2006, 45(10): 807-810.
  18. 18. 　Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis[J]. N Engl J Med, 1994, 331(19): 1286-1292.
  19. 19. 　Tomita H, Egashira K, Ohara Y, et al. Early induction of transforming growth factor-beta via angiotensin Ⅱ type 1 receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis in rats[J]. Hypertension, 1998, 32(2): 273-279.
  20. 20. 　Verheule S, Sato T, Everett T 4th, et al. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1[J]. Circ Res, 2004, 94(11): 1458-1465.
  21. 21. 　Darbar D, Motsinger AA, Ritchie MD, et al. Polymorphism modulates symptomatic response to antiarrhythmic drug therapy in patients with lone atrial fibrillation[J]. Heart Rhythm, 2007, 4(6): 743-749.
  22. 22. 　Boldt A, Wetzel U, Weigl J, et al. Expression of angiotensin Ⅱreceptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease[J]. J Am Coll Cardiol, 2003, 42(10): 1785-1792.
  23. 23. 　Psychari SN, Apostolou TS, Sinos L, et al. Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation[J]. Am J Cardiol, 2005, 95(6): 764-767.
  24. 24. 　Sawaya SE, Rajawat YS, Rami TG, et al. Downregulation of connexin40 and increased prevalence of atrial arrhythmias in transgenic mice with cardiac-restricted overexpression of tumor necrosis factor[J]. Am J Physiol Heart Circ Physiol, 2007, 292(3): H1561-H1567.
  25. 25. 　Marín F, Corral J, Roldán V, et al. FactorⅩ Val34Leu polymorphism modulates the prothrombotic and inflammatory state associated with atrial fibrillation[J]. J Mol Cell Cardiol, 2004, 37(3): 699-704.
  26. 26. 　Aviles RJ, Martin DO, Apperson-Hansen C. Inflammation as a risk factor for atrial fibrillation[J]. Circulation, 2004, 13(3): 64.
  27. 27. 　Dernellis J, Panaretou M. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation[J]. Eur Heart J, 2004, 25(13): 1100-1107.
  28. 28. 　Santangeli P, Ferrante G, Pelargonio G, et al. Usefulness of statins in preventing atrial fibrillation in patients with permanent pacemaker: a systematic review[J]. Europace, 2010, 12(5): 649-654.
  29. 29. 　Shiroshita-Takeshita A, Schram G, Lavoie J, et al. Effect of simvastatin and antioxidant vitamins on atrial fibrillation promotion by atrial-tachycardia remodeling in dogs[J]. Circulation, 2004, 110(16): 2313-2319.
  30. 30. 　Armaganijan L, Eikelboom J, Healey JS, et al. New pharmacotherapy for stroke prevention in atrial fibrillation: Update 2010[J]. Adv Ther, 2009, 26(12): 1058-1071.
  31. 31. 　Tops LF, Schalij MJ, Bax JJ. Imaging and atrial fibrillation: the role of multimodality imaging in patient evaluation and management of atrial fibrillation[J]. Eur Heart J, 2010, 31(5): 542-551.
  32. 32. 　Nademanee K, Lockwood E, Oketani N, et al. Catheter ablation of atrial fibrillation guided by complex fractionated atrial electrogram mapping of atrial fibrillation substrate[J]. J Cardiol, 2010, 55(1): 1-12.
  33. 33. 　殷躍輝, 劉增長, 吳近近, 等. 胺碘酮與氯沙坦、培哚普利聯(lián)合治療陣發(fā)性心房顫動的前瞻、隨機開發(fā)研究[J]. 中華心血管病雜志, 2006, 34(4): 299-301.
  34. 34. 　Doughty MJ, Jonuscheit S. The orbscan acoustic (correction) factor for central corneal thickness measures of normal human corneas[J]. Eye Contact Lens, 2010, 36(2): 106-115.
  35. 35. 　Tsai CT, Lai LP, Lin JL, et al. Renin-angiotensin system gene polymorphisms and atrial fibrillation[J]. Circulation, 2004, 109(13): 1640-1646.
  36. 36. 　Firouzi M, Ramanna H, Kok B, et al. Association of human connexin40 gene polymorphisms with atrial vulnerability as a risk factor for idiopathic atrial fibrillation[J]. Circ Res, 2004, 95(4): e29-e33.
  37. 37. 　Schreieck J, Dostal S, von Beckerath N, et al. C825T polymorphism of the G-protein beta3 subunit gene and atrial fibrillation: association of the TT genotype with a reduced risk for atrial fibrillation[J]. Am Heart J, 2004, 148(3): 545-550.