• 南京大學(xué)醫(yī)學(xué)院臨床學(xué)院 南京軍區(qū)南京總醫(yī)院呼吸科（江蘇南京 210002）通訊作者：施毅，E-mail：shichen56@hotmail.com;

丙酮酸是糖酵解的終產(chǎn)物及三羧酸循環(huán)的起始物，是機(jī)體能量代謝的主要中間產(chǎn)物，當(dāng)機(jī)體氧供應(yīng)充足時(shí)丙酮酸在線粒體內(nèi)氧化為乙酰輔酶A，維持三羧酸循環(huán)；當(dāng)氧供應(yīng)不足時(shí)在乳酸脫氫酶作用下直接轉(zhuǎn)化成乳酸，迅速為機(jī)體供能。丙酮酸在細(xì)胞內(nèi)可能作為內(nèi)源性抗氧化物，無(wú)需酶就能降解過(guò)氧化氫，產(chǎn)生二氧化碳和水。丙酮酸消除過(guò)氧化氫的反應(yīng)高效迅速。除了清除過(guò)氧化氫，丙酮酸也能清除羥基、一氧化氮等其他活性氧。丙酮酸乙酯（EP）是丙酮酸親脂性的酯化物，在抗炎、抗凝及安全性方面明顯優(yōu)于丙酮酸[1]

引用本文： 林心情,施毅. 丙酮酸乙酯對(duì)膿毒癥保護(hù)作用研究進(jìn)展. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2008, 08(5): 394-397. doi: 復(fù)制

1. Fink MP.Ethyl pyruvate：a novel anti-inflammatory agent.J Intern Med，2007，261：349-362.
2. Salahudeen AK，Clark EC，Nath KA.Hydrogen peroxide-induced renal injury.A protective role for pyruvate in vitro and in vivo.J Clin Invest，1991，88：1886-1893.
3. 張凱倫，郭家龍，孫宗全，等.丙酮酸乙酯預(yù)先給藥對(duì)大鼠離體心臟缺血再灌注損傷的影響.中華麻醉學(xué)雜志，2007，27：717-720.
4. Uchiyama T，Delude RL，F(xiàn)ink MP.Dose-dependent effects of ethyl pyruvate in mice subjected to mesenteric ischemia and reperfusion.Intensive Care Med，2003，29：2050-2058.
5. Tsung A，Kaizu T，Nakao A，et al.Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptosis.Transplantation，2005，79：196-204.
6. Zeng J，Liu J，Yang GY，et al.Exogenous ethyl pyruvate versus pyruvate during metabolic recovery after oxidative stress in neonatal rat cerebrocortical slices.Anesthesiology，2007，107：630-640.
7. Sims CA，Wattanasirichaigoon S，Menconi MJ，et al.Ringer’s ethyl pyruvate solution ameliorates ischemia/reperfusion-induced intestinal mucosal injury in rats.Crit Care Med，2001，29：1513-1518.
8. Yang R，Gallo DJ，Baust JJ，et al.Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock.Am J Physiol Gastrointest Liver Physiol，2002，283：G212-G221.
9. Su F，Wang Z，Cai Y，et al.Beneficial effects of ethyl pyruvate in septic shock from peritonitis.Arch Surg，2007，142：166-171.
10. 寇秋野，管向東.丙酮酸乙酯對(duì)膿毒性休克犬氧代謝及組織灌注指標(biāo)的影響.中國(guó)危重病急救醫(yī)學(xué)，2008，20：34-36.
11. Khatri M，Sharma JM.Infectious bursal disease virus infection induces macrophage activation via p38 MAPK and NF-kappaB pathway.Virus Res，2006，118：70-77.
12. Ulloa L，Ochani M，Yang H，et al.Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation.Proc Natl Acad Sci USA，2002，99：12351-12356.
13. 李錕，吳承堂，丘雪紅.丙酮酸乙酯對(duì)嚴(yán)重腹腔感染時(shí)腸黏膜過(guò)氧化損傷的防治作用.中國(guó)危重病急救醫(yī)學(xué)，2006，18：154-156.
14. Song M，Kellum JA，Kaldas H，et al.Evidence that glutathione depletion is a mechanism responsible for the anti-inflammatory effects of ethyl pyruvate in cultured LPS-stimulated RAW 264.7 cells.J Pharmacol Exp Ther，2004，308：307-316.
15. Parikh AA，Moon MR，Pritts TA，et al.IL-1beta induction of NF-kappaB activation in human intestinal epithelial cells is independent of oxyradical signaling.Shock，2000，13：8-13.
16. Salzman AL，Denenberg AG，Ueta I，et al.Induction and activity of nitric oxide synthase in cultured human intestinal epithelial monolayers.Am J Physiol，1996，270：G565-G573.
17. Sappington PL，Han X，Yang R，et al.Ethyl pyruvate ameliorates intestinal epithelial barrier dysfunction in endotoxemic mice and immunostimulated Caco-2 enterocytic monolayers.J Pharmacol Exp Ther，2003，304：464-476.
18. Bowie AG，Moynagh PN，O’Neill LAJ.Lipid peroxidation is involved in the activation of NF-κB by tumor necrosis factor but not interleukin-1 in the human endothelial cell line ECV304.J Biol Chem，1997，272：25941-25950.
19. Chandel NS，Trzyna WC，McClintock DS，et al.Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin.J Immunol，2000，165：1013-1021.
20. Sappington PL，F(xiàn)ink ME，Yang R，et al.Ethyl pyruvate provides durable protection against inflammationinduced intestinal epithelial barrier dysfunction.Shock，2003，20：521-528.
21. Venkataraman R，Kellum JA，Song M，et al.Resuscitation with Ringer’s ethyl pyruvate solution prolongs survival and modulates plasma cytokine and nitrite/nitrate concentrations in a rat model of lipopolysaccharide-induced shock.Shock，2002，18：507-512.
22. Tsai BM，Lahm T，Morrell ED，et al.Ethyl pyruvate inhibits hypoxic pulmonary vasoconstriction and attenuates pulmonary artery cytokine expression.J Surg Res，2008，145：130-134.
23. Wang H，Li W，Goldstein R，et al.HMGB1 as a potential therapeutic target.Novartis Found Symp，2007，280：73-85.
24. 楊智勇，凌燕，陶京，等.延遲的丙酮酸乙酯治療對(duì)重癥急性胰腺炎大鼠胰外臟器損傷的影響及其機(jī)制.世界華人消化雜志，2007，15：2638-2642.
25. Lim SC，Choi JE，Kim CH，et al.Ethyl pyruvate induces necrosis-to-apoptosis switch and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells.Int J Mol Med，2007，20：187-192.
26. Park JS，Gamboni-Robertson F，He Q，et al.High mobility group box 1 protein interacts with multiple Toll-like receptors.Am J Physiol Cell Physiol，2006，290：C917-C924.
27. van Zoelen MA，Bakhtiari K，Dessing MC et al.Ethyl pyruvate exerts combined anti-inflammatory and anticoagulant effects on human monocytic cells.Thromb Haemost，2006，96：789-793.
28. Miyaji T，Hu X，Yuen PST，et al.Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice.Kidney Int，2003，64：1620-1631.
29. Hauser B，Kick J，Asfar P，et al.Ethyl pyruvate improves systemic and hepato-splanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.Crit Care Med，2005，33：2034-2042.
30. Yang R，Uchiyama T，Alber SM，et al.Ethyl pyruvate ameliorates distant organ injury in a murine model of acute necrotizing pancreatitis.Crit Care Med，2004，32：1453-1459.
31. 曾漣，姚尚龍，楊艷.丙酮酸乙酯對(duì)大鼠膿毒癥肺損傷的保護(hù)作用.中國(guó)急救醫(yī)學(xué)，2005，25：725-727.
32. Kim JB，Yu YM，Kim SW，et al.Anti-inflammatory mechanism is involved in ethyl pyruvate-mediated efficacious neuroprotection in the postischemic brain.Brain Res，2005，1060：188-192.
33. Cho IH，Kim SW，Kim JB，et al.Ethyl pyruvate attenuates kainic acid-induced neuronal cell death in the mouse hippocampus.J Neurosci Res，2006，84：1505-1511.
34. Karabeyoglu M，Unal B，Bozkurt B，et al，The effect of ethyl pyruvate on oxidative stress in intestine and bacterial translocation after thermal injury.J Surg Res，2008，144：59-63.
35. Fink MP.Ethyl pyruvare：a novel treatment for sepsis.Current Drug Targets，2007，8：515-518.
  1. 1. Fink MP.Ethyl pyruvate：a novel anti-inflammatory agent.J Intern Med，2007，261：349-362.
  2. 2. Salahudeen AK，Clark EC，Nath KA.Hydrogen peroxide-induced renal injury.A protective role for pyruvate in vitro and in vivo.J Clin Invest，1991，88：1886-1893.
  3. 3. 張凱倫，郭家龍，孫宗全，等.丙酮酸乙酯預(yù)先給藥對(duì)大鼠離體心臟缺血再灌注損傷的影響.中華麻醉學(xué)雜志，2007，27：717-720.
  4. 4. Uchiyama T，Delude RL，F(xiàn)ink MP.Dose-dependent effects of ethyl pyruvate in mice subjected to mesenteric ischemia and reperfusion.Intensive Care Med，2003，29：2050-2058.
  5. 5. Tsung A，Kaizu T，Nakao A，et al.Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptosis.Transplantation，2005，79：196-204.
  6. 6. Zeng J，Liu J，Yang GY，et al.Exogenous ethyl pyruvate versus pyruvate during metabolic recovery after oxidative stress in neonatal rat cerebrocortical slices.Anesthesiology，2007，107：630-640.
  7. 7. Sims CA，Wattanasirichaigoon S，Menconi MJ，et al.Ringer’s ethyl pyruvate solution ameliorates ischemia/reperfusion-induced intestinal mucosal injury in rats.Crit Care Med，2001，29：1513-1518.
  8. 8. Yang R，Gallo DJ，Baust JJ，et al.Ethyl pyruvate modulates inflammatory gene expression in mice subjected to hemorrhagic shock.Am J Physiol Gastrointest Liver Physiol，2002，283：G212-G221.
  9. 9. Su F，Wang Z，Cai Y，et al.Beneficial effects of ethyl pyruvate in septic shock from peritonitis.Arch Surg，2007，142：166-171.
  10. 10. 寇秋野，管向東.丙酮酸乙酯對(duì)膿毒性休克犬氧代謝及組織灌注指標(biāo)的影響.中國(guó)危重病急救醫(yī)學(xué)，2008，20：34-36.
  11. 11. Khatri M，Sharma JM.Infectious bursal disease virus infection induces macrophage activation via p38 MAPK and NF-kappaB pathway.Virus Res，2006，118：70-77.
  12. 12. Ulloa L，Ochani M，Yang H，et al.Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation.Proc Natl Acad Sci USA，2002，99：12351-12356.
  13. 13. 李錕，吳承堂，丘雪紅.丙酮酸乙酯對(duì)嚴(yán)重腹腔感染時(shí)腸黏膜過(guò)氧化損傷的防治作用.中國(guó)危重病急救醫(yī)學(xué)，2006，18：154-156.
  14. 14. Song M，Kellum JA，Kaldas H，et al.Evidence that glutathione depletion is a mechanism responsible for the anti-inflammatory effects of ethyl pyruvate in cultured LPS-stimulated RAW 264.7 cells.J Pharmacol Exp Ther，2004，308：307-316.
  15. 15. Parikh AA，Moon MR，Pritts TA，et al.IL-1beta induction of NF-kappaB activation in human intestinal epithelial cells is independent of oxyradical signaling.Shock，2000，13：8-13.
  16. 16. Salzman AL，Denenberg AG，Ueta I，et al.Induction and activity of nitric oxide synthase in cultured human intestinal epithelial monolayers.Am J Physiol，1996，270：G565-G573.
  17. 17. Sappington PL，Han X，Yang R，et al.Ethyl pyruvate ameliorates intestinal epithelial barrier dysfunction in endotoxemic mice and immunostimulated Caco-2 enterocytic monolayers.J Pharmacol Exp Ther，2003，304：464-476.
  18. 18. Bowie AG，Moynagh PN，O’Neill LAJ.Lipid peroxidation is involved in the activation of NF-κB by tumor necrosis factor but not interleukin-1 in the human endothelial cell line ECV304.J Biol Chem，1997，272：25941-25950.
  19. 19. Chandel NS，Trzyna WC，McClintock DS，et al.Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin.J Immunol，2000，165：1013-1021.
  20. 20. Sappington PL，F(xiàn)ink ME，Yang R，et al.Ethyl pyruvate provides durable protection against inflammationinduced intestinal epithelial barrier dysfunction.Shock，2003，20：521-528.
  21. 21. Venkataraman R，Kellum JA，Song M，et al.Resuscitation with Ringer’s ethyl pyruvate solution prolongs survival and modulates plasma cytokine and nitrite/nitrate concentrations in a rat model of lipopolysaccharide-induced shock.Shock，2002，18：507-512.
  22. 22. Tsai BM，Lahm T，Morrell ED，et al.Ethyl pyruvate inhibits hypoxic pulmonary vasoconstriction and attenuates pulmonary artery cytokine expression.J Surg Res，2008，145：130-134.
  23. 23. Wang H，Li W，Goldstein R，et al.HMGB1 as a potential therapeutic target.Novartis Found Symp，2007，280：73-85.
  24. 24. 楊智勇，凌燕，陶京，等.延遲的丙酮酸乙酯治療對(duì)重癥急性胰腺炎大鼠胰外臟器損傷的影響及其機(jī)制.世界華人消化雜志，2007，15：2638-2642.
  25. 25. Lim SC，Choi JE，Kim CH，et al.Ethyl pyruvate induces necrosis-to-apoptosis switch and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells.Int J Mol Med，2007，20：187-192.
  26. 26. Park JS，Gamboni-Robertson F，He Q，et al.High mobility group box 1 protein interacts with multiple Toll-like receptors.Am J Physiol Cell Physiol，2006，290：C917-C924.
  27. 27. van Zoelen MA，Bakhtiari K，Dessing MC et al.Ethyl pyruvate exerts combined anti-inflammatory and anticoagulant effects on human monocytic cells.Thromb Haemost，2006，96：789-793.
  28. 28. Miyaji T，Hu X，Yuen PST，et al.Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice.Kidney Int，2003，64：1620-1631.
  29. 29. Hauser B，Kick J，Asfar P，et al.Ethyl pyruvate improves systemic and hepato-splanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.Crit Care Med，2005，33：2034-2042.
  30. 30. Yang R，Uchiyama T，Alber SM，et al.Ethyl pyruvate ameliorates distant organ injury in a murine model of acute necrotizing pancreatitis.Crit Care Med，2004，32：1453-1459.
  31. 31. 曾漣，姚尚龍，楊艷.丙酮酸乙酯對(duì)大鼠膿毒癥肺損傷的保護(hù)作用.中國(guó)急救醫(yī)學(xué)，2005，25：725-727.
  32. 32. Kim JB，Yu YM，Kim SW，et al.Anti-inflammatory mechanism is involved in ethyl pyruvate-mediated efficacious neuroprotection in the postischemic brain.Brain Res，2005，1060：188-192.
  33. 33. Cho IH，Kim SW，Kim JB，et al.Ethyl pyruvate attenuates kainic acid-induced neuronal cell death in the mouse hippocampus.J Neurosci Res，2006，84：1505-1511.
  34. 34. Karabeyoglu M，Unal B，Bozkurt B，et al，The effect of ethyl pyruvate on oxidative stress in intestine and bacterial translocation after thermal injury.J Surg Res，2008，144：59-63.
  35. 35. Fink MP.Ethyl pyruvare：a novel treatment for sepsis.Current Drug Targets，2007，8：515-518.

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