丙酮酸乙酯對膿毒癥保護作用研究進展_《中國呼吸與危重監護雜志》

作者：

林心情 ,  施毅

南京大學醫學院臨床學院南京軍區南京總醫院呼吸科（江蘇南京 210002）通訊作者：施毅，E-mail：shichen56@hotmail.com;

關鍵詞：

丙酮酸乙酯膿毒癥

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丙酮酸是糖酵解的終產物及三羧酸循環的起始物，是機體能量代謝的主要中間產物，當機體氧供應充足時丙酮酸在線粒體內氧化為乙酰輔酶A，維持三羧酸循環；當氧供應不足時在乳酸脫氫酶作用下直接轉化成乳酸，迅速為機體供能。丙酮酸在細胞內可能作為內源性抗氧化物，無需酶就能降解過氧化氫，產生二氧化碳和水。丙酮酸消除過氧化氫的反應高效迅速。除了清除過氧化氫，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于丙酮酸[1]

引用本文： 林心情,施毅. 丙酮酸乙酯對膿毒癥保護作用研究進展. 中國呼吸與危重監護雜志, 2008, 08(5): 394-397. doi: 復制

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.丙酮酸乙酯預先給藥對大鼠離體心臟缺血再灌注損傷的影響.中華麻醉學雜志，2007，27：717-720.
4.	Uchiyama T，Delude RL，Fink 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.丙酮酸乙酯對膿毒性休克犬氧代謝及組織灌注指標的影響.中國危重病急救醫學，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.丙酮酸乙酯對嚴重腹腔感染時腸黏膜過氧化損傷的防治作用.中國危重病急救醫學，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，Fink 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重癥急性胰腺炎大鼠胰外臟器損傷的影響及其機制.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.丙酮酸乙酯對大鼠膿毒癥肺損傷的保護作用.中國急救醫學，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. 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.丙酮酸乙酯預先給藥對大鼠離體心臟缺血再灌注損傷的影響.中華麻醉學雜志，2007，27：717-720.
4. Uchiyama T，Delude RL，Fink 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.丙酮酸乙酯對膿毒性休克犬氧代謝及組織灌注指標的影響.中國危重病急救醫學，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.丙酮酸乙酯對嚴重腹腔感染時腸黏膜過氧化損傷的防治作用.中國危重病急救醫學，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，Fink 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重癥急性胰腺炎大鼠胰外臟器損傷的影響及其機制.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.丙酮酸乙酯對大鼠膿毒癥肺損傷的保護作用.中國急救醫學，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.

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《中國呼吸與危重監護雜志》

丙酮酸乙酯對膿毒癥保護作用研究進展

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