丙酮酸乙酯对脓毒症保护作用研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

林心情 ,  施毅

Corresponding author：

施毅, Email: shichen56@hotmail.com

Keywords：

丙酮酸乙酯; 脓毒症

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丙酮酸是糖酵解的终产物及三羧酸循环的起始物，是机体能量代谢的主要中间产物，当机体氧供应充足时丙酮酸在线粒体内氧化为乙酰辅酶A，维持三羧酸循环；当氧供应不足时在乳酸脱氢酶作用下直接转化成乳酸，迅速为机体供能。丙酮酸在细胞内可能作为内源性抗氧化物，无需酶就能降解过氧化氢，产生二氧化碳和水。丙酮酸消除过氧化氢的反应高效迅速。除了清除过氧化氢，丙酮酸也能清除羟基、一氧化氮等其他活性氧。丙酮酸乙酯（EP）是丙酮酸亲脂性的酯化物，在抗炎、抗凝及安全性方面明显优于丙酮酸[1]

Citation： 林心情,施毅. 丙酮酸乙酯对脓毒症保护作用研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2008, 08(5): 394-397. doi: Copy

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.	张凯伦，郭家龙，孙宗全，等.丙酮酸乙酯预先给药对大鼠离体心脏缺血再灌注损伤的影响.中华麻醉学杂志，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，管向东.丙酮酸乙酯对脓毒性休克犬氧代谢及组织灌注指标的影响.中国危重病急救医学，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.	李锟，吴承堂，丘雪红.丙酮酸乙酯对严重腹腔感染时肠黏膜过氧化损伤的防治作用.中国危重病急救医学，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.	杨智勇，凌燕，陶京，等.延迟的丙酮酸乙酯治疗对重症急性胰腺炎大鼠胰外脏器损伤的影响及其机制.世界华人消化杂志，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.	曾涟，姚尚龙，杨艳.丙酮酸乙酯对大鼠脓毒症肺损伤的保护作用.中国急救医学，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. 张凯伦，郭家龙，孙宗全，等.丙酮酸乙酯预先给药对大鼠离体心脏缺血再灌注损伤的影响.中华麻醉学杂志，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，管向东.丙酮酸乙酯对脓毒性休克犬氧代谢及组织灌注指标的影响.中国危重病急救医学，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. 李锟，吴承堂，丘雪红.丙酮酸乙酯对严重腹腔感染时肠黏膜过氧化损伤的防治作用.中国危重病急救医学，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. 杨智勇，凌燕，陶京，等.延迟的丙酮酸乙酯治疗对重症急性胰腺炎大鼠胰外脏器损伤的影响及其机制.世界华人消化杂志，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. 曾涟，姚尚龙，杨艳.丙酮酸乙酯对大鼠脓毒症肺损伤的保护作用.中国急救医学，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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