• 1 四川大學(xué)華西醫(yī)院麻醉科（成都， 610041）; 2 瀘州醫(yī)學(xué)院附屬醫(yī)院麻醉科;

【摘要】 瞬時(shí)受體電位香草酸亞型1（transient receptor potential vaniuoed 1，TRPV1）是非選擇性陽離子通道，可被多種配體及刺激激活。TRPV1在組織缺血再灌注損傷（ischemia-reprefusion injury，IRI）中的作用已在多個(gè)器管中被證實(shí)。現(xiàn)就對TRPV1在IRI中的病理生理機(jī)制及TRPV1激動(dòng)劑在肺IRI中的保護(hù)作用及應(yīng)用價(jià)值進(jìn)行綜述。

引用本文： 王茂華,基鵬,王儒蓉. 瞬時(shí)受體電位香草酸亞型1激動(dòng)劑在肺缺血再灌注損傷保護(hù)中的應(yīng)用前景. 華西醫(yī)學(xué), 2011, 26(1): 121-124. doi: 復(fù)制

1. 　Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway[J]. Nature, 1997, 389(6653): 816-824.
2. 　Welch JM, Simon SA, Reinhart PH. The activation mechanism of rat vanilloid receptor 1 by capsaicin involves the pore domain and differs from the activation by either acid or heat[J]. Proc Natl Acal Sci USA, 2000, 97(25): 13889-13894.
3. 　Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms[J]. Pharmacol Rev, 1999, 51(2): 159-212.
4. 　Tominaga M, Wada M, Masu M. Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia[J]. Proc Natl Acal Sci USA, 2001, 98(12): 6951-6956.
5. 　Sugiura T, Tominaga M, Katsuya H, et al. Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1[J]. J Neurophysiology, 2002, 88(1): 544-548.
6. 　Veronesi B, Oortgiesen M. The TRPV1 receptor: Target of toxicants and therapeutics[J]. Toxicol Sci, 2006, 89(1): 1-3.
7. 　Aviado DM, Guevara Aviado D. The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes[J]. Ann NY Acad Sci, 2001, 940: 48-58.
8. 　Wisskirchen FM, Burt RP, Marshall I. Pharmacological characterization of CGRP receptors mediating relaxation of the rat pulmonary artery and inhibition of twitch responses of the rat vas deferens[J]. Br J Pharmacol, 1998, 123(8): 1673-1683.
9. 　Eppinger MJ, Jones ML, Deeb GM, et al. Pattern of injury and the role of neutrophils in reperfusion injury of rat lung[J]. J Surg Res, 1995, 58(6): 713-718.
10. 　Eppinger MJ, Deeb GM, Bolling SF, et al. Mediators of ischemia-reperfusion injury of rat lung[J]. Am J Pathol, 1997, 150(5): 1773-1784.
11. 　Yu CC, Lai YL. In vivo pressure-flow curve in unilateral rat lung ischemia-reperfusion injury[J]. J Appl Physiol, 2001, 90(5): 1865-1870.
12. 　Iwazaki S, Takeyoshi I, Ohwada S, et al. FR128998 (a PAF receptor antagonist) counters the increased pulmonary vascular resistance associated with ischemia-reperfusion injury in the canine lung[J]. Int J Angiol, 2001, 10(1): 10-14.
13. 　Sunose Y, Takeyoshi I, Tsutsumi H, et al. Effects of FK3311 on pulmonary ischemiareperfusion injury in a canine model[J]. J Surg Res, 2001, 95(2): 167-173.
14. 　Gilmont RR, Dardano A, Engle JS, et al. TNF-alpha potentiates oxidant and reperfusion-induced endothelial cell injury[J]. J Surg Res, 1996, 61(1): 175-182.
15. 　Fiser SM, Tribble CG, Long SM, et al. Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response[J]. J Thorac Cardiovasc Surg, 2001, 121 (6): 1069-1075.
16. 　de Perrot M, Sekine Y, Fischer S, et al. Interleukin-8 release during early reperfusion predicts s graft function in human lung transplantation[J]. Am J Respir Crit Care Med, 2002, 165 (2): 211-215.
17. 　de Perrot M, Young K, Imai Y, et al. Recipient T cells mediate reperfusion injury after lung t ransplantation in t he rat[J]. J Immunol, 2003, 171(10): 4995-5002.
18. 　Eppinger MJ, Jones ML, Deeb GM, et al. Pattern of injury and the role of neutrophils in reperfusion injury of rat lung[J]. J Surg Res, 1995, 58(6): 713-718.
19. 　Naidu BV, Woolley SM, Farivar A, et al. Early tumor necrosis factor-α release from the pulmonary macrophage in lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg, 2004, 127(5): 1502-1508.
20. 　Sekido N, Mukaida N, Harada A, et al. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8[J]. Nature, 1993, 365(6447): 654-657.
21. 　Hosenpud JD, Bennett LE, Keck BM, et al. The Registry of the International Society for Heart and Iung Transplantation: seventeenth official report: 2 000[J]. J Heart Lung Transplant, 2000, 19 (10): 909-931.
22. 　Farivar AS, Krishnadasan B, Naidu BV, et al. Endogenous interleukin-4 and interleukin-10 regulate experimental lung ischemia reperfusion injury[J]. Ann Thorac Surg, 2003, 76 (1): 253-259.
23. 　de Perrot M, Fischer S, Liu M, et al. Impact of human interleukin-10 on vector-induced inflammation and early graft function in rat lung transplantation[J]. Am J Respir Cell Mol Biol, 2003, 28 (5): 616-625.
24. 　Ohmi H, chiara K, Abiko Y. Role of oxygen radicals in canine myocardial metabolic derangement during regional ischemia[J]. Am J Physiology, 1992, 262 (2 pt 2): 553-561.
25. 　Ikeda H, Suzuki Y, Koike M, et al. Apoptosis is a major mode of cell death caused by ischemia and ischemia/reperfusion injury to the rat intestinal epithelium[J]. Gut, 1998, 42(4): 530-537.
26. 　Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock[J]. Ann Rev Pharmacol Toxicol, 1993, 33: 71-90.
27. 　Taghavi S, Abraham D, Riml P, et al. Co-expression of endothelin-1 and vascular endothelial growth factor mediates increased vascular permeability in lung graft s before reperfusion[J]. J Heart Lung Transplant, 2002, 21 (5): 600-603.
28. 　Abraham D, Taghavi S, Riml P, et al. VEGF-A and -C but not -B mediate incraesed vascular permeability in preserved lung grafts[J]. Transplantation, 2002, 73 (11): 1703-1706.
29. 　Shaw MJ, Shennib H, Bousette N, et al. Effect of endothelin receptor antagonist on lung allograft apoptosis and NOSII expression[J]. Ann Thorac Surg, 2001, 72(2): 386-390.
30. 　Vainikka TL, Heikkila LJ, Kukkonen S, et al. Inhaled NO and prostacyclin during porcine single lung transplantation[J]. Ann Thorac Surg, 2001, 72(6): 1892-1897.
31. 　Kao SJ, Peng TC, Lee RP, et al. Nitric oxide mediates lung injury induced by ischemia-reperfusion in rats[J]. J Biomed Sci, 2003, 10(1): 58-64.
32. 　Wang LH, Wang DH. TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice[J]. Circulation, 2005, 112(23): 3617-3623.
33. 　秦素蘭, 劉陜嶺, 王儒蓉. 辣椒素對大鼠心肌缺血再灌注損傷保護(hù)作用的研究[J]. 四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2008, 39(4): 350-554.
34. 　Yao L, Shao L, Sun Z, et al. Decreased expression of transient receptor potentialvanilloid 1 impairs the postischemic recovery of diabetic mouse hearts[J]. Circulation, 2009, 73(6): 1127-1132.
35. 　Harada N, Okajima K, Yuksel M, et al. Contribution of capsaicin sensitive sensory neurons to antithrombin-induced reduction of ischemia/reperfusion-induced liver injury in rats[J]. Thromb Haemost, 2005, 93(1): 48-56.
36. 　Wang LH, Luo M, Wang Y, et al. Impaired vasodilation in response to perivascular nerve stimulation in mesenteric arteries of TRPV1-null mutant mice[J]. J Hypertens, 2006, 24(12): 2399-2408.
37. 　Okajima K, Isobe H, Uchiba M, et al. Role of sensory neuron in reduction of endotoxin-induced hypotension in rats[J]. Crit Care Med, 2005, 33(4): 847-854.
38. 　Ueda K, Tsuji F, Hirata T, et al. Preventive effect of TRPV1 agonists capsaicin and resiniferatoxin on ischemia/reperfusion-induced renal injury in rats[J]. J Cardiovasc Pharmacol, 2008, 51(5): 513-520.
39. 　Mizutani A, Okajima K, Murakami K, et al. Activation of Sensory Neurons Reduces Ischemia/Reperfusion-induced Acute Renal Injury in Rats[J]. Anesthesiology, 2009, 110(2): 361-369.
40. 　Torii H, Hosoi J, Beissert S, et al. Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide[J]. J Leukoc Biol, 1997, 61(2): 216-223.
41. 　Springer J, Geppetti P, Fischer A, et al. Calcitonin gene-related peptide as inflammatory mediator [J]. Pulm Pharmacol Ther, 2003, 16(3): 121-130.
42. 　Monneret G, Arpin M, Venet F, et al. Calcitonin gene related peptide and N-procalcitonin modulate CDllb upregulation in lipopoly- saccharide activated monocytes and neutrophils [J]. Intensive Care Med, 2003, 29(6): 923.
43. 　Demirbilek S, Ersoy MO, Demirbilek S, et al. Small-dose capsaicin reduces systemic inflammatory responses in septic rats[J]. Anesth Analg, 2004, 99(5): 1501-1507.
44. 　Bucinskaite V, Brodda G, Stenfors C, et al. Increased concentrations of calcitonin gene-related peptide immunoreactivity in rat brain and peripheral tissue after ischemia: correlation to flap survival[J]. Neuropetides, 1998, 32(2): 179-183.
45. 　Tjen-A-Looi S, Ekman R, Lippton H, et al. CGRP and somatostatin modulate chronic hypoxic pulmonary hypertension[J]. Am J Physiol, 1992, 263 (3 pt 2): 681-690.
46. 　Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages[J]. Biochim Biophys Acta, 1994, 1224(2): 255-263.
47. 　Kogure K, Goto S, Nishimura M, et al. Mechanism of potent antiperoxidative effect of capsaicin[J]. Biochim Biophys Acta, 2002, 1573(1): 84-92.
  1. 1. 　Caterina MJ, Schumacher MA, Tominaga M, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway[J]. Nature, 1997, 389(6653): 816-824.
  2. 2. 　Welch JM, Simon SA, Reinhart PH. The activation mechanism of rat vanilloid receptor 1 by capsaicin involves the pore domain and differs from the activation by either acid or heat[J]. Proc Natl Acal Sci USA, 2000, 97(25): 13889-13894.
  3. 3. 　Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms[J]. Pharmacol Rev, 1999, 51(2): 159-212.
  4. 4. 　Tominaga M, Wada M, Masu M. Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia[J]. Proc Natl Acal Sci USA, 2001, 98(12): 6951-6956.
  5. 5. 　Sugiura T, Tominaga M, Katsuya H, et al. Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1[J]. J Neurophysiology, 2002, 88(1): 544-548.
  6. 6. 　Veronesi B, Oortgiesen M. The TRPV1 receptor: Target of toxicants and therapeutics[J]. Toxicol Sci, 2006, 89(1): 1-3.
  7. 7. 　Aviado DM, Guevara Aviado D. The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes[J]. Ann NY Acad Sci, 2001, 940: 48-58.
  8. 8. 　Wisskirchen FM, Burt RP, Marshall I. Pharmacological characterization of CGRP receptors mediating relaxation of the rat pulmonary artery and inhibition of twitch responses of the rat vas deferens[J]. Br J Pharmacol, 1998, 123(8): 1673-1683.
  9. 9. 　Eppinger MJ, Jones ML, Deeb GM, et al. Pattern of injury and the role of neutrophils in reperfusion injury of rat lung[J]. J Surg Res, 1995, 58(6): 713-718.
  10. 10. 　Eppinger MJ, Deeb GM, Bolling SF, et al. Mediators of ischemia-reperfusion injury of rat lung[J]. Am J Pathol, 1997, 150(5): 1773-1784.
  11. 11. 　Yu CC, Lai YL. In vivo pressure-flow curve in unilateral rat lung ischemia-reperfusion injury[J]. J Appl Physiol, 2001, 90(5): 1865-1870.
  12. 12. 　Iwazaki S, Takeyoshi I, Ohwada S, et al. FR128998 (a PAF receptor antagonist) counters the increased pulmonary vascular resistance associated with ischemia-reperfusion injury in the canine lung[J]. Int J Angiol, 2001, 10(1): 10-14.
  13. 13. 　Sunose Y, Takeyoshi I, Tsutsumi H, et al. Effects of FK3311 on pulmonary ischemiareperfusion injury in a canine model[J]. J Surg Res, 2001, 95(2): 167-173.
  14. 14. 　Gilmont RR, Dardano A, Engle JS, et al. TNF-alpha potentiates oxidant and reperfusion-induced endothelial cell injury[J]. J Surg Res, 1996, 61(1): 175-182.
  15. 15. 　Fiser SM, Tribble CG, Long SM, et al. Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response[J]. J Thorac Cardiovasc Surg, 2001, 121 (6): 1069-1075.
  16. 16. 　de Perrot M, Sekine Y, Fischer S, et al. Interleukin-8 release during early reperfusion predicts s graft function in human lung transplantation[J]. Am J Respir Crit Care Med, 2002, 165 (2): 211-215.
  17. 17. 　de Perrot M, Young K, Imai Y, et al. Recipient T cells mediate reperfusion injury after lung t ransplantation in t he rat[J]. J Immunol, 2003, 171(10): 4995-5002.
  18. 18. 　Eppinger MJ, Jones ML, Deeb GM, et al. Pattern of injury and the role of neutrophils in reperfusion injury of rat lung[J]. J Surg Res, 1995, 58(6): 713-718.
  19. 19. 　Naidu BV, Woolley SM, Farivar A, et al. Early tumor necrosis factor-α release from the pulmonary macrophage in lung ischemia-reperfusion injury[J]. J Thorac Cardiovasc Surg, 2004, 127(5): 1502-1508.
  20. 20. 　Sekido N, Mukaida N, Harada A, et al. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8[J]. Nature, 1993, 365(6447): 654-657.
  21. 21. 　Hosenpud JD, Bennett LE, Keck BM, et al. The Registry of the International Society for Heart and Iung Transplantation: seventeenth official report: 2 000[J]. J Heart Lung Transplant, 2000, 19 (10): 909-931.
  22. 22. 　Farivar AS, Krishnadasan B, Naidu BV, et al. Endogenous interleukin-4 and interleukin-10 regulate experimental lung ischemia reperfusion injury[J]. Ann Thorac Surg, 2003, 76 (1): 253-259.
  23. 23. 　de Perrot M, Fischer S, Liu M, et al. Impact of human interleukin-10 on vector-induced inflammation and early graft function in rat lung transplantation[J]. Am J Respir Cell Mol Biol, 2003, 28 (5): 616-625.
  24. 24. 　Ohmi H, chiara K, Abiko Y. Role of oxygen radicals in canine myocardial metabolic derangement during regional ischemia[J]. Am J Physiology, 1992, 262 (2 pt 2): 553-561.
  25. 25. 　Ikeda H, Suzuki Y, Koike M, et al. Apoptosis is a major mode of cell death caused by ischemia and ischemia/reperfusion injury to the rat intestinal epithelium[J]. Gut, 1998, 42(4): 530-537.
  26. 26. 　Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock[J]. Ann Rev Pharmacol Toxicol, 1993, 33: 71-90.
  27. 27. 　Taghavi S, Abraham D, Riml P, et al. Co-expression of endothelin-1 and vascular endothelial growth factor mediates increased vascular permeability in lung graft s before reperfusion[J]. J Heart Lung Transplant, 2002, 21 (5): 600-603.
  28. 28. 　Abraham D, Taghavi S, Riml P, et al. VEGF-A and -C but not -B mediate incraesed vascular permeability in preserved lung grafts[J]. Transplantation, 2002, 73 (11): 1703-1706.
  29. 29. 　Shaw MJ, Shennib H, Bousette N, et al. Effect of endothelin receptor antagonist on lung allograft apoptosis and NOSII expression[J]. Ann Thorac Surg, 2001, 72(2): 386-390.
  30. 30. 　Vainikka TL, Heikkila LJ, Kukkonen S, et al. Inhaled NO and prostacyclin during porcine single lung transplantation[J]. Ann Thorac Surg, 2001, 72(6): 1892-1897.
  31. 31. 　Kao SJ, Peng TC, Lee RP, et al. Nitric oxide mediates lung injury induced by ischemia-reperfusion in rats[J]. J Biomed Sci, 2003, 10(1): 58-64.
  32. 32. 　Wang LH, Wang DH. TRPV1 gene knockout impairs postischemic recovery in isolated perfused heart in mice[J]. Circulation, 2005, 112(23): 3617-3623.
  33. 33. 　秦素蘭, 劉陜嶺, 王儒蓉. 辣椒素對大鼠心肌缺血再灌注損傷保護(hù)作用的研究[J]. 四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2008, 39(4): 350-554.
  34. 34. 　Yao L, Shao L, Sun Z, et al. Decreased expression of transient receptor potentialvanilloid 1 impairs the postischemic recovery of diabetic mouse hearts[J]. Circulation, 2009, 73(6): 1127-1132.
  35. 35. 　Harada N, Okajima K, Yuksel M, et al. Contribution of capsaicin sensitive sensory neurons to antithrombin-induced reduction of ischemia/reperfusion-induced liver injury in rats[J]. Thromb Haemost, 2005, 93(1): 48-56.
  36. 36. 　Wang LH, Luo M, Wang Y, et al. Impaired vasodilation in response to perivascular nerve stimulation in mesenteric arteries of TRPV1-null mutant mice[J]. J Hypertens, 2006, 24(12): 2399-2408.
  37. 37. 　Okajima K, Isobe H, Uchiba M, et al. Role of sensory neuron in reduction of endotoxin-induced hypotension in rats[J]. Crit Care Med, 2005, 33(4): 847-854.
  38. 38. 　Ueda K, Tsuji F, Hirata T, et al. Preventive effect of TRPV1 agonists capsaicin and resiniferatoxin on ischemia/reperfusion-induced renal injury in rats[J]. J Cardiovasc Pharmacol, 2008, 51(5): 513-520.
  39. 39. 　Mizutani A, Okajima K, Murakami K, et al. Activation of Sensory Neurons Reduces Ischemia/Reperfusion-induced Acute Renal Injury in Rats[J]. Anesthesiology, 2009, 110(2): 361-369.
  40. 40. 　Torii H, Hosoi J, Beissert S, et al. Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide[J]. J Leukoc Biol, 1997, 61(2): 216-223.
  41. 41. 　Springer J, Geppetti P, Fischer A, et al. Calcitonin gene-related peptide as inflammatory mediator [J]. Pulm Pharmacol Ther, 2003, 16(3): 121-130.
  42. 42. 　Monneret G, Arpin M, Venet F, et al. Calcitonin gene related peptide and N-procalcitonin modulate CDllb upregulation in lipopoly- saccharide activated monocytes and neutrophils [J]. Intensive Care Med, 2003, 29(6): 923.
  43. 43. 　Demirbilek S, Ersoy MO, Demirbilek S, et al. Small-dose capsaicin reduces systemic inflammatory responses in septic rats[J]. Anesth Analg, 2004, 99(5): 1501-1507.
  44. 44. 　Bucinskaite V, Brodda G, Stenfors C, et al. Increased concentrations of calcitonin gene-related peptide immunoreactivity in rat brain and peripheral tissue after ischemia: correlation to flap survival[J]. Neuropetides, 1998, 32(2): 179-183.
  45. 45. 　Tjen-A-Looi S, Ekman R, Lippton H, et al. CGRP and somatostatin modulate chronic hypoxic pulmonary hypertension[J]. Am J Physiol, 1992, 263 (3 pt 2): 681-690.
  46. 46. 　Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages[J]. Biochim Biophys Acta, 1994, 1224(2): 255-263.
  47. 47. 　Kogure K, Goto S, Nishimura M, et al. Mechanism of potent antiperoxidative effect of capsaicin[J]. Biochim Biophys Acta, 2002, 1573(1): 84-92.