左旋精氨酸及硝基左旋精氨酸对内毒素休克大鼠转归的影响
作者：肖南 刘韧 田昆仑 刘萍 刁有芳 陈惠孙
单位：第三军医大学大坪医院野战外科研究所，重庆400042
关键词：一氧化氮；内毒素休克；左旋精氨酸；硝基左旋精氨酸
创伤外科杂志000312摘 要：目的一氧化氮(NitricOxide，NO)在感染性休克中具有多种作用，但其对休克转归的影响目前仍不清楚。本研究用NO产生的前体物质L-arg和其抑制剂NNLA从正反两个方面探讨其对内毒休克大鼠转归的影响。方法实验大鼠分为生理盐水对照组(NS)、内毒素(10mg/kg，ip)组(ETX)、内毒素+NNLA(4mg/kg，ip)组、内毒素+L-arg(40mg/kg，ip)组和内毒素+NNLA+Lar-g组。上述处理后，测定大鼠不同时间的平均动脉压(meanarterialpressure，MAP)、血浆NO水平(NO2-/NO3-)以及24小时存活率。结果内毒素休克大鼠，血浆NO2-/NO3-明显增加，同时MAP降低，NNLA虽可抑制NO产生，升高MAP，但显著降低12小时和24小时存活率；而L-arg虽不能升高MAP，但可使其维持稳定，且24小时存活率明显提高。结论在本实验条件下，NO对内毒素休克可能有有利作用，抑制NO合成则对休克的转归不利。
, http://www.100md.com
分类号：R605.971.05 文献标识码：A
文章编号：1009-4237(2000)03-0162-03
Effect of L-arginine and N-nitro-L-arginine on the outcome in endotoxic shock rat
XIAO Nan,LIU Ren,TIAN kun-lun
(Research Institute of Surgery, Daping Hospital, Third Military University, Chongqing 400042)
Abstract：Objective Nitric oxide(NO) has several pathophysiological effects on septic shock, however, its effect on the outcome of septic sbock is still contrasty. This study was to evaluate NO effect on the outcome in endotoxic shock rat by using L-arg, the precursor of NO, and NNLA, the inhibitor of NO formation. Methods A total of 213 rats, weighing 180-230g, were subjected to this study. The animals were divided into normal saline control(NS), endotoxin(ETX, LPS 10mg/kg, ip), ETX+NNLA(4mg/kg, ip), ETX+L-arg(40mg/kg, ip), and ETX+NNLA+L-arg groups. MAP was monitored, 24 hour survival rate and the level of plasma NO2-/NO3-, the stable metabolic end products of NO, were determined. Results Plasma NO2-/NO3- significantly increased and MAP gradually decreased after ETX administration. Although inhibition of NO production with NNLA could significantly increase MAP at early phase, it remarkably decrease 12 and 24 hour survival rate, Administration of L-arg could, however, maintain MAP at late phase and significantly improve 24 survival rate. Conclusion NO may have beneficial effect on the outcome of endotoxic shock in the study and inhibition of NO production may be detrimental.
, 百拇医药
Keywords：nitric oxide; endotoxic shock; L-arginine; N-nirto-L-arginine
参考文献：
[1]Stoclet JC, Muller B, Andriantsitohaina R, et al. Overproduction of nitric oxide in pathophysiology of blood vessels[J]. Biolchemistry, 1998,63(7):826-832.
[2]Kuhl SJ, Rosen H. Nitric oxide and septic shock. From bench to bedsidea[J]. West J Med, 1998,168(3):176-181.
[3]Mercy J, Traber LD, Nelson, et al. Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis[J]. J Appl Physiol, 1992,73(2):324-326.
, http://www.100md.com
[4]Hegesh E, Shiload J. Blood nitrates and infantile methemoglobinemia[J]. Clin Chim Acta, 1982, 125(1):107-112.
[5]Kirkebn KA, Strand OA. The role of nitric oxide in sepsisan overview[J]. Acta Anaesthesiol Scand, 1999,43(3):275-288.
[6]Vodovotz Y, Kopp JB, Takegucbi H, et al. Increased mortality, blunted production of nitric oxide, and increased production of TNF - α in endotoxemic TGF - β transgenic mice[J]. J Leukoc Biol, 1998,63(1):31-39.
, 百拇医药
[7]Avontuur JA, Tutein Nolthenius RP, van Bodegom JW, et al. Prolonged inhibition of nitric oxide synthesis in severe septic shock: a clinical study[J]. Crit Care Med, 1998,26(4):660-667.
[8]Kumins NH, Hunt J, Gamelli RL, et al. Molsidomine increases endotoxic survival and decreeases cytokine production[J]. Shock, 1997,7(3):200-205.
[9]Strand OA, Leone AM, Giercksky KE, et al. N (G)- monomethyl-l-arginine improves survival in a pig model of abdominal sepsis[J]. Crit Care Med, 1998,26(9):1490-1499.
, 百拇医药
[10]Wolkow PP. Involvement and bual effects of nitric oxide in septic shock[J]. Inflamm Res, 1998,47(4):152-166.
[11]Liaudet L, Rosselet A, Schaller MD, et al. Nonselective versus selective inhitition of inducible nitric oxide synthase in experimental endotoxic shock[J]. J Infect Dis, 1998,177(1):127-132.
[12]Wray GM, Millar CG, Hinds CJ, et al. Selective inhitibion of the activity of inducible nitric oxide synthase prevents the circulatory failure, but not the organ injury/dysfunction, caused by endotoxin[J]. Shock, 1998,9(5):329-335.
[13]肖南，陈惠孙，胡德耀，等.一氧化氮对大鼠内毒素血症肠道的保护作用及机理研究[J].中国病理生理杂志，1997，13(6)：677-680.
收稿日期：1999-08-28
修稿日期：1999-11-02, http://www.100md.com
单位：第三军医大学大坪医院野战外科研究所，重庆400042
关键词：一氧化氮；内毒素休克；左旋精氨酸；硝基左旋精氨酸
创伤外科杂志000312摘 要：目的一氧化氮(NitricOxide，NO)在感染性休克中具有多种作用，但其对休克转归的影响目前仍不清楚。本研究用NO产生的前体物质L-arg和其抑制剂NNLA从正反两个方面探讨其对内毒休克大鼠转归的影响。方法实验大鼠分为生理盐水对照组(NS)、内毒素(10mg/kg，ip)组(ETX)、内毒素+NNLA(4mg/kg，ip)组、内毒素+L-arg(40mg/kg，ip)组和内毒素+NNLA+Lar-g组。上述处理后，测定大鼠不同时间的平均动脉压(meanarterialpressure，MAP)、血浆NO水平(NO2-/NO3-)以及24小时存活率。结果内毒素休克大鼠，血浆NO2-/NO3-明显增加，同时MAP降低，NNLA虽可抑制NO产生，升高MAP，但显著降低12小时和24小时存活率；而L-arg虽不能升高MAP，但可使其维持稳定，且24小时存活率明显提高。结论在本实验条件下，NO对内毒素休克可能有有利作用，抑制NO合成则对休克的转归不利。
, http://www.100md.com
分类号：R605.971.05 文献标识码：A
文章编号：1009-4237(2000)03-0162-03
Effect of L-arginine and N-nitro-L-arginine on the outcome in endotoxic shock rat
XIAO Nan,LIU Ren,TIAN kun-lun
(Research Institute of Surgery, Daping Hospital, Third Military University, Chongqing 400042)
Abstract：Objective Nitric oxide(NO) has several pathophysiological effects on septic shock, however, its effect on the outcome of septic sbock is still contrasty. This study was to evaluate NO effect on the outcome in endotoxic shock rat by using L-arg, the precursor of NO, and NNLA, the inhibitor of NO formation. Methods A total of 213 rats, weighing 180-230g, were subjected to this study. The animals were divided into normal saline control(NS), endotoxin(ETX, LPS 10mg/kg, ip), ETX+NNLA(4mg/kg, ip), ETX+L-arg(40mg/kg, ip), and ETX+NNLA+L-arg groups. MAP was monitored, 24 hour survival rate and the level of plasma NO2-/NO3-, the stable metabolic end products of NO, were determined. Results Plasma NO2-/NO3- significantly increased and MAP gradually decreased after ETX administration. Although inhibition of NO production with NNLA could significantly increase MAP at early phase, it remarkably decrease 12 and 24 hour survival rate, Administration of L-arg could, however, maintain MAP at late phase and significantly improve 24 survival rate. Conclusion NO may have beneficial effect on the outcome of endotoxic shock in the study and inhibition of NO production may be detrimental.
, 百拇医药
Keywords：nitric oxide; endotoxic shock; L-arginine; N-nirto-L-arginine
参考文献：
[1]Stoclet JC, Muller B, Andriantsitohaina R, et al. Overproduction of nitric oxide in pathophysiology of blood vessels[J]. Biolchemistry, 1998,63(7):826-832.
[2]Kuhl SJ, Rosen H. Nitric oxide and septic shock. From bench to bedsidea[J]. West J Med, 1998,168(3):176-181.
[3]Mercy J, Traber LD, Nelson, et al. Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis[J]. J Appl Physiol, 1992,73(2):324-326.
, http://www.100md.com
[4]Hegesh E, Shiload J. Blood nitrates and infantile methemoglobinemia[J]. Clin Chim Acta, 1982, 125(1):107-112.
[5]Kirkebn KA, Strand OA. The role of nitric oxide in sepsisan overview[J]. Acta Anaesthesiol Scand, 1999,43(3):275-288.
[6]Vodovotz Y, Kopp JB, Takegucbi H, et al. Increased mortality, blunted production of nitric oxide, and increased production of TNF - α in endotoxemic TGF - β transgenic mice[J]. J Leukoc Biol, 1998,63(1):31-39.
, 百拇医药
[7]Avontuur JA, Tutein Nolthenius RP, van Bodegom JW, et al. Prolonged inhibition of nitric oxide synthesis in severe septic shock: a clinical study[J]. Crit Care Med, 1998,26(4):660-667.
[8]Kumins NH, Hunt J, Gamelli RL, et al. Molsidomine increases endotoxic survival and decreeases cytokine production[J]. Shock, 1997,7(3):200-205.
[9]Strand OA, Leone AM, Giercksky KE, et al. N (G)- monomethyl-l-arginine improves survival in a pig model of abdominal sepsis[J]. Crit Care Med, 1998,26(9):1490-1499.
, 百拇医药
[10]Wolkow PP. Involvement and bual effects of nitric oxide in septic shock[J]. Inflamm Res, 1998,47(4):152-166.
[11]Liaudet L, Rosselet A, Schaller MD, et al. Nonselective versus selective inhitition of inducible nitric oxide synthase in experimental endotoxic shock[J]. J Infect Dis, 1998,177(1):127-132.
[12]Wray GM, Millar CG, Hinds CJ, et al. Selective inhitibion of the activity of inducible nitric oxide synthase prevents the circulatory failure, but not the organ injury/dysfunction, caused by endotoxin[J]. Shock, 1998,9(5):329-335.
[13]肖南，陈惠孙，胡德耀，等.一氧化氮对大鼠内毒素血症肠道的保护作用及机理研究[J].中国病理生理杂志，1997，13(6)：677-680.
收稿日期：1999-08-28
修稿日期：1999-11-02, http://www.100md.com