体外循环中L-精氨酸对胰岛素抵抗和炎性因子的作用及相关性研究
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摘要
胰岛素抵抗是指胰岛素在促进组织细胞摄取和利用葡萄糖时,需要超常量的胰岛素才能引起正常量反应的一种状态。研究发现,体外循环过程中由于创伤、麻醉、低温、低压、血液稀释、非搏动性灌流等因素造成强烈的应激反应,导致血中葡萄糖、游离脂肪酸、乳酸、甘油浓度增加,抑制了胰岛素在外周组织细胞胰岛素受体、胰岛素受体底物-1和细胞分裂活化蛋白激酶的磷酸化作用,同时应激也可导致肾上腺皮质激素升高,间接加重高血糖和胰岛素抵抗[1]。随着心肺转流下心脏瓣膜置换术的广泛开展,体外循环期间胰岛素抵抗的发生引起广泛关注。采用抗炎手段调控炎性反应程度,有助于缓解胰岛素抵抗[2]。L-精氨酸是一种人体必需氨基酸,在细胞的一氧化氮(N0)、肌酸、聚胺等的生物合成过程中发挥重要作用。其通过一氧化氮合成酶形成一氧化氮及肌氨酸,一氧化氮通过其强大的舒张血管、抗血栓、抑制血管平滑肌增殖、对抗氧自由基及抑制中性粒细胞与内皮细胞的粘附和减轻心脏手术的炎症反应,从而减轻心脏缺血再灌注损伤。
目的:本临床研究通过观察L-精氨酸对体外循环术中、术后肿瘤坏死因子-a、白介素-6、白介素-8、胰岛素抵抗的影响,探讨L-精氨酸对体外循环中胰岛素抵抗的影响,并且探究炎性因子在其中的作用。
方法:将40例拟行心脏瓣膜置换术的心脏病患者术前随机分为两组:(1)处理组(A组n=20),主动脉开放前10分钟给予100mg/kg精氨酸;(2)对照组(B组n=20),两组分别于麻醉前、体外循环后15min、升主动脉阻断开放后15 min和停体外循环后2小时采血,用酶联免疫吸附法测肿瘤坏死因子-a、白介素-6、白介素-8、胰岛素,氧化酶法测血糖。
结果:两组病例肿瘤坏死因子-a、白介素-6、白介素-8水平,麻醉前均较低,组间无显著性差异(P>0.05);体外循环后15 min、升主动脉阻断开放后15 min和停体外循环后2小时肿瘤坏死因子-a、白介素-6、白介素-8水平与同组术前比较均有明显升高(P<0.01);升主动脉阻断开放后15 min和停体外循环后2小时肿瘤坏死因子-a、白介素-6、白介素-8水平A组与B组相比有显著性降低(P<0.01)。两组病例血糖、胰岛素从手术开始逐渐升高,到CPB主动脉开放后达到高峰,之后稍有回落,但是仍然高于术前水平。两组CPB后15分钟及CPB主动脉阻断开放后15分钟、CPB结束2小时血糖水平与同组麻醉前比较均有明显升高(P<0.01);而且同组CPB主动脉阻断开放后15分钟与CPB后15分钟比较有明显的升高(P<0.01)。两组病例胰岛素抵抗指数麻醉前均较低,组间无显著性差异(P>0.05);体外循环后15 min、升主动脉阻断开放后15 min和停体外循环后2小时与同组术前比较均有明显升高(P<0.01);升主动脉阻断开放后15 min和停体外循环后2小时A组与B组相比有显著性降低(P<0.01)。两组病例胰岛素敏感指数麻醉前,组间无显著性差异(P>0.05);体外循环后15 min、升主动脉阻断开放后15 min和停体外循环后2小时与同组术前比较均有明显降低(P<0.01);升主动脉阻断开放后15 min和停体外循环后2小时A组与B组相比有显著性差异(P<0.01)。肿瘤坏死因子-a、白介素-6、白介素-8与胰岛素敏感指数相关分析显示具有负相关关系,肿瘤坏死因子-a、白介素-6、白介素-8与胰岛素抵抗指数相关分析显示具有正相关关系。
结论:1.体外循环可引起肿瘤坏死因子-a、白介素-6、白介素-8血浆水平的显著性升高。2.体外循环可引起血糖、胰岛素水平升高。3.体外循环可加重胰岛素抵抗程度。4.L-精氨酸可以降低体外循环中肿瘤坏死因子-a、白介素-6、白介素-8血浆水平,具有抗炎作用。5.L-精氨酸可以缓解胰岛素抵抗程度。6.炎性因子与胰岛素敏感性存在负相关关系。7.炎性因子与胰岛素抵抗存在正相关关系。
Insulin resistance means a state that insulin in the promotion of tissue glucose uptake and utilization, needing for extraordinary volume than the normal amount of insulin can cause response. The study found, in cardiopulmonary bypass process such as low temperature, low pressure, blood dilution, non-pulsatile perfusion, and anesthesia can cause a strong stress response, resulting in blood glucose, free fatty acids, glycerol and lactic acid concentration increasing, inhibition of insulin in peripheral tissue insulin receptor, insulin receptor substrate -1 and activated protein kinase phosphorylation, and stress also can result in increased adrenocorticotropic hormone and indirectly increase the high blood glucose and insulin resistance [1].With cardiopulmonary bypass cardiac valve replacement under a wide range of conduct, the occurrence of insulin resistance caused wide concern in cardiopulmonary bypass period. Means to control degree of inflammatory reaction help alleviate the insulin resistance [2].L-arginine is an essential amino acids in nitric oxide, creatine, polyamine biosynthesis of the cells ,and plays an important role in the body.L-arginine synthases nitric oxide and citrulline through nitric oxide synthetase. Nitric oxide can lead to strong vascular relaxing, anti-thrombosis, inhibition of vascular smooth muscle proliferation, inhibition of free radical oxidation and neutrophils to endothelial cells,and reducing inflammatory response and cardiac ischemia-reperfusion injury in cardiopulmonary bypass.
Purpose: This clinical study of L-arginine in cardiopulmonary bypass, we observe tumor necrosis factor-a, interlukin-6, interlukin-8, insulin resistance.Purpose is to investigate L-arginine effect insulin resistance on during cardiopulmonary bypass and proinflammatory cytokine and explore the role of inflammatory factor .
Methods: 40 cases of heart valve replacement patients were randomly divided into two groups before operation:(1) treatment group (A group n = 20),10 minutes before the aorta declamping L-arginine of 100mg/kg is used;(2) control group (B group n = 20),blood sample of the two groups were collected in pre-anesthesia, 15 min after cardiopulmonary bypass ,15 min after the ascending aorta declamping and two hours after weaning off pump. using enzyme-linked immunosorbent assay measure tumor necrosis factor-a,interlukin-6, interlukin-8,insulin,and oxidase method measure blood glucose.
Results: The two cases of tumor necrosis factor-a, interlukin-6, interlukin-8 levels were lower before anesthesia, there were no significant differences (P> 0.05); 15 min after cardiopulmonary bypass,ascending aorta declamping and 2 hours after weaning off pump tumor necrosis factor-a,interlukin-6,interlukin-8 levels compared with the preoperative group are significantly higher (P<0.01);15 min after ascending aorta declamping and 2 hours after weaning off pump tumor necrosis factor-a,interlikin-6,interlukin-8 level of A group and B group were significantly lower (P <0.01). Two cases of blood glucose, insulin gradually increased from surgery to 15 min after the ascending aorta declamping and then post-CPB decline slightly, but still higher than the preoperative level. The two groups 15min after CPB, the 15 min after the ascending aorta declamping, 2 hours post-CPB compared with pre- anesthesia the blood glucose level were significantly higher (P <0.01); and the 15 min after the ascending aorta declamping compared with 15 min after CPB was significantly increased (P <0.01).two cases of insulin resistance index was lower before anesthesia, there were no significant differences (P>0.05);15min after cardiopulmonary bypass,15 min after the ascending aorta declamping and two hours after weaning off pump compared with the preoperative were significantly higher (P <0.01);15 min after ascending aorta declamping, 2 hours after weaning off pump the A group is compared to B group and shows a significant decrease (P <0.01).two cases of insulin sensitivity index before anesthesia, there were no significant differences (P>0.05);15min after cardiopulmonary bypass,15 min after the ascending aorta declamping and two hours after weaning off pump compared with the preoperative were significantly lower (P <0.01);15 min after ascending aorta declamping, 2 hours after weaning off pump the A group is compared to B group shows a significantly lower (P <0.01). Proinflammatory cytokine and insulin sensitivity is exitting a passive correlation. Proinflammatory cytokine and insulin resistance is exitting a positive correlation.
Conclusion:
Through this study can come to following conclusions:
1.Cardiopulmonary bypass can cause tumor necrosis factor-a, interlukin-6, interlukin-8 blood Plasma levels to increase.
2. Cardiopulmonary bypass can cause hyperglycemia,hyperinsulinemia.
2.Cardiopulmonary bypass can deepen degree of insulin resistance.
3.L-arginine after cardiopulmonary bypass can reduce Tumor necrosis factor-a, interlukin-6,interlukin-8 level.
4.L-arginine can alleviate the degree of insulin resistance.
5.Proinflammatory cytokine and insulin sensitivity is exitting a passive correlation
6. Proinflammatory cytokine and insulin resistance is exitting a positive correlation
目的:本临床研究通过观察L-精氨酸对体外循环术中、术后肿瘤坏死因子-a、白介素-6、白介素-8、胰岛素抵抗的影响,探讨L-精氨酸对体外循环中胰岛素抵抗的影响,并且探究炎性因子在其中的作用。
方法:将40例拟行心脏瓣膜置换术的心脏病患者术前随机分为两组:(1)处理组(A组n=20),主动脉开放前10分钟给予100mg/kg精氨酸;(2)对照组(B组n=20),两组分别于麻醉前、体外循环后15min、升主动脉阻断开放后15 min和停体外循环后2小时采血,用酶联免疫吸附法测肿瘤坏死因子-a、白介素-6、白介素-8、胰岛素,氧化酶法测血糖。
结果:两组病例肿瘤坏死因子-a、白介素-6、白介素-8水平,麻醉前均较低,组间无显著性差异(P>0.05);体外循环后15 min、升主动脉阻断开放后15 min和停体外循环后2小时肿瘤坏死因子-a、白介素-6、白介素-8水平与同组术前比较均有明显升高(P<0.01);升主动脉阻断开放后15 min和停体外循环后2小时肿瘤坏死因子-a、白介素-6、白介素-8水平A组与B组相比有显著性降低(P<0.01)。两组病例血糖、胰岛素从手术开始逐渐升高,到CPB主动脉开放后达到高峰,之后稍有回落,但是仍然高于术前水平。两组CPB后15分钟及CPB主动脉阻断开放后15分钟、CPB结束2小时血糖水平与同组麻醉前比较均有明显升高(P<0.01);而且同组CPB主动脉阻断开放后15分钟与CPB后15分钟比较有明显的升高(P<0.01)。两组病例胰岛素抵抗指数麻醉前均较低,组间无显著性差异(P>0.05);体外循环后15 min、升主动脉阻断开放后15 min和停体外循环后2小时与同组术前比较均有明显升高(P<0.01);升主动脉阻断开放后15 min和停体外循环后2小时A组与B组相比有显著性降低(P<0.01)。两组病例胰岛素敏感指数麻醉前,组间无显著性差异(P>0.05);体外循环后15 min、升主动脉阻断开放后15 min和停体外循环后2小时与同组术前比较均有明显降低(P<0.01);升主动脉阻断开放后15 min和停体外循环后2小时A组与B组相比有显著性差异(P<0.01)。肿瘤坏死因子-a、白介素-6、白介素-8与胰岛素敏感指数相关分析显示具有负相关关系,肿瘤坏死因子-a、白介素-6、白介素-8与胰岛素抵抗指数相关分析显示具有正相关关系。
结论:1.体外循环可引起肿瘤坏死因子-a、白介素-6、白介素-8血浆水平的显著性升高。2.体外循环可引起血糖、胰岛素水平升高。3.体外循环可加重胰岛素抵抗程度。4.L-精氨酸可以降低体外循环中肿瘤坏死因子-a、白介素-6、白介素-8血浆水平,具有抗炎作用。5.L-精氨酸可以缓解胰岛素抵抗程度。6.炎性因子与胰岛素敏感性存在负相关关系。7.炎性因子与胰岛素抵抗存在正相关关系。
Insulin resistance means a state that insulin in the promotion of tissue glucose uptake and utilization, needing for extraordinary volume than the normal amount of insulin can cause response. The study found, in cardiopulmonary bypass process such as low temperature, low pressure, blood dilution, non-pulsatile perfusion, and anesthesia can cause a strong stress response, resulting in blood glucose, free fatty acids, glycerol and lactic acid concentration increasing, inhibition of insulin in peripheral tissue insulin receptor, insulin receptor substrate -1 and activated protein kinase phosphorylation, and stress also can result in increased adrenocorticotropic hormone and indirectly increase the high blood glucose and insulin resistance [1].With cardiopulmonary bypass cardiac valve replacement under a wide range of conduct, the occurrence of insulin resistance caused wide concern in cardiopulmonary bypass period. Means to control degree of inflammatory reaction help alleviate the insulin resistance [2].L-arginine is an essential amino acids in nitric oxide, creatine, polyamine biosynthesis of the cells ,and plays an important role in the body.L-arginine synthases nitric oxide and citrulline through nitric oxide synthetase. Nitric oxide can lead to strong vascular relaxing, anti-thrombosis, inhibition of vascular smooth muscle proliferation, inhibition of free radical oxidation and neutrophils to endothelial cells,and reducing inflammatory response and cardiac ischemia-reperfusion injury in cardiopulmonary bypass.
Purpose: This clinical study of L-arginine in cardiopulmonary bypass, we observe tumor necrosis factor-a, interlukin-6, interlukin-8, insulin resistance.Purpose is to investigate L-arginine effect insulin resistance on during cardiopulmonary bypass and proinflammatory cytokine and explore the role of inflammatory factor .
Methods: 40 cases of heart valve replacement patients were randomly divided into two groups before operation:(1) treatment group (A group n = 20),10 minutes before the aorta declamping L-arginine of 100mg/kg is used;(2) control group (B group n = 20),blood sample of the two groups were collected in pre-anesthesia, 15 min after cardiopulmonary bypass ,15 min after the ascending aorta declamping and two hours after weaning off pump. using enzyme-linked immunosorbent assay measure tumor necrosis factor-a,interlukin-6, interlukin-8,insulin,and oxidase method measure blood glucose.
Results: The two cases of tumor necrosis factor-a, interlukin-6, interlukin-8 levels were lower before anesthesia, there were no significant differences (P> 0.05); 15 min after cardiopulmonary bypass,ascending aorta declamping and 2 hours after weaning off pump tumor necrosis factor-a,interlukin-6,interlukin-8 levels compared with the preoperative group are significantly higher (P<0.01);15 min after ascending aorta declamping and 2 hours after weaning off pump tumor necrosis factor-a,interlikin-6,interlukin-8 level of A group and B group were significantly lower (P <0.01). Two cases of blood glucose, insulin gradually increased from surgery to 15 min after the ascending aorta declamping and then post-CPB decline slightly, but still higher than the preoperative level. The two groups 15min after CPB, the 15 min after the ascending aorta declamping, 2 hours post-CPB compared with pre- anesthesia the blood glucose level were significantly higher (P <0.01); and the 15 min after the ascending aorta declamping compared with 15 min after CPB was significantly increased (P <0.01).two cases of insulin resistance index was lower before anesthesia, there were no significant differences (P>0.05);15min after cardiopulmonary bypass,15 min after the ascending aorta declamping and two hours after weaning off pump compared with the preoperative were significantly higher (P <0.01);15 min after ascending aorta declamping, 2 hours after weaning off pump the A group is compared to B group and shows a significant decrease (P <0.01).two cases of insulin sensitivity index before anesthesia, there were no significant differences (P>0.05);15min after cardiopulmonary bypass,15 min after the ascending aorta declamping and two hours after weaning off pump compared with the preoperative were significantly lower (P <0.01);15 min after ascending aorta declamping, 2 hours after weaning off pump the A group is compared to B group shows a significantly lower (P <0.01). Proinflammatory cytokine and insulin sensitivity is exitting a passive correlation. Proinflammatory cytokine and insulin resistance is exitting a positive correlation.
Conclusion:
Through this study can come to following conclusions:
1.Cardiopulmonary bypass can cause tumor necrosis factor-a, interlukin-6, interlukin-8 blood Plasma levels to increase.
2. Cardiopulmonary bypass can cause hyperglycemia,hyperinsulinemia.
2.Cardiopulmonary bypass can deepen degree of insulin resistance.
3.L-arginine after cardiopulmonary bypass can reduce Tumor necrosis factor-a, interlukin-6,interlukin-8 level.
4.L-arginine can alleviate the degree of insulin resistance.
5.Proinflammatory cytokine and insulin sensitivity is exitting a passive correlation
6. Proinflammatory cytokine and insulin resistance is exitting a positive correlation
引文
[1] Finney ST,Zekveld C,Elia A,etal.Glucose control and mortality in critically ill patients[J]JAMA,2003,290:2 041-2 047
[2]薛纪秀,范隆,徐国勋,等.丙泊酚和异氟醚麻醉对胰岛素抵抗及促炎细胞因子的影响[J].临床麻醉学杂志,2008,1,12(1):8-10
[3] Fernandez-Veledo S,HernandezR,TeruelT,etal.Ceramidemediates TNF-alpha-induced insulin resistance on GLUT4 gene expression in brown adipocytes[J]. Arch PhysiolBiochem, 2006, 112(1): 13-22.
[4] JoveM,PlanavilaA,Sanchez R M,etal. Palmitate induces tumor necrosis factor-alpha expression in C2C12skeletalmuscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation[J]. Endocrinology, 2006, 147(1): 552-561.
[5] Kim HE,Tumour necrosis factor-alpha-induced glucose-stimulated insulin secretion inhibition in INS-1 cells is ascribed to a reduction of the glucose-stimulated Ca2+ influx. J Endocrinol. 2008 Sep;198(3):549-60. Epub 2008 Jul 1.
[6] Aljada A,Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells Metabolism. 2002 Apr;51(4):487-91.
[7] Gravlee GP,Davis RF,Utley JR,etal.Cardiopulmonary bypass:principles and practice. Baltimore:williams &wilkins, 1993. 513-519.
[8]隋东虎,石应康,王儒蓉,等.体外循环缺血一再灌注后心肌胰岛素抵抗现象的初步研究.中国胸心血管外科临床杂志,2001,8(1)28-31.10.
[9]隋东虎,石应康,王儒蓉,等.体外循环缺血一再灌注后心肌胰岛素抵抗与心功能障碍的关系.中华实验外科杂志,2002,19(3):208-210.
[10] PietersenHGLnagenbergCJGeskesG,etal.Myoeardial substrate uptake and oxidation during and after routin cardiac surgery . JThorae cardlovaseSurg,1999,118(l):71一80.
[11]王天龙,于德水,张京范.心脏外科围术期应用尼卡地平对心肌能量代谢的影响.中华麻醉学杂志,2001,1(2):73一76.
[12] Cendan JC,MD,SoubaWW,MD,ScD,etal. Cytokines regulate endotoxin stimulation of endothelial cell arginine transport.Surgery1995;117:213一9.
[13] Engelman DT,MD,Watanable M,MD Manlik N,PhD,etal.L-Arginine reduces endothelial inflammation and myocardialStunning during ischemial reperfusion.Ann Thoracsurg1995;60:1275一81.
[14] Angele MK,MD,Smail N,MD,Ayala A,PhD,etal.L-Arginine: a unique amino acid for restoring the depressed macrophage functions after trauma-hemorrhage.Jtrauma1999:46(1):34-9.
[15] Hiramatsu T,MD,Forbess JM,MD,Miura T,MD,etal.Effects of L-arginine and L-nitro-arginine methyl ester on recovery of neonatal lamb hearts after cold ischemia.JThoracCardiovace Surg1995;109:81-1.
[16]熊卫明,邱建,李志梁,等L-精氨酸对体外循环后血浆细胞因子及肌钙蛋白的影响[J]使用医学杂志,2003,15(5)474-475.
[17]林丽娜,王万铁,徐正衸等.左旋精氨酸对体外循环缺血再灌注损伤心肌的保护作用[J]中国胸心血管外科临床杂志,2000,5(2):89
[18]杜智勇,史忠,杨天德,等.体外循环心内直视术中胰岛素受体TPK活性的变化及意义[J].体外循环杂志,2002,4:81-87.
[19] Kuntschen FR,Galletti PM,Hahn C,etal. Alterations of insulin and glucose metabolism during cardiopulmonary bypass under normothermia[J]. J. Thorac Cardiovascu Surg. 1985,89:97-106.
[20]Kuntschen F R,Galletti PM,Hahn C,etal.Glucose-insulin interactions during cardiopulmonary bypass. Hypothermia versus normothermia[J]. J. Thorac Cardiovascu Surg. 1986,91:451-459.
[21] Lehot J J, PirizH,Villard J,etal. Glucose homeostasis. Comparison between hypothermic and normothermic cardiopulmonary bypass[J]. Chest. 1992 Jul; 102(1): 106-11 .
[22]体外循环研究与实践(龙村主编)[M].北京医科大学出版社,2000,58.
[23]徐建军,陈琳,胡大仁,等.体外循环手术病人胰腺内、外分泌功能的变化[J].江西医学院学报2000.12.31; 40(4): 25-27.
[24] McKnight C K,ElliottM J,Pearson DT,et al. The effects of four different crystalloid bypass pump-priming fluids upon the metabol response to cardiac operation[J]. J-Thorac-Cardiovasc-Surg1985 Jul; 90(1): 97-111.
[25] Sebel PS,Bovill J G, SchellekensAP,et al. Hormonal responses to high-dose fentanyl anaesthesia. Astudy in patients undergoing cardiac surgery[J]. Br-J-Anaesth. 1981 Sep; 53(9): 941-948.
[26]黑飞龙,龚菁,胡强等.围体外循环期肿瘤坏死因子与胰岛素抵抗[J].中国体外循环杂志, 2003, 1: 72-74.
[27] Mescheryakov AV,Kozlov I A, Dementyeva I I,et al. Glucose metabolism and insulin activity during cardiac surgery[J]. J-Cardiothorac-Anesth. 1989 Oct; 3(5): 536-543.
[28] McPheed,S J.etal. Pathophisiology of Disease[J]. (3rd version). McGraw-Hill,2000, 434-436.
[29]杜智勇.应激与胰岛素抵抗[M].国外医学·麻醉学与复苏分册2001.02.15; 22(1): 10-13.
[30] Takayama S,Kahn C R,Kubo K,et al. Alterations in insulin receptor autophosphorylation in insulin resistance: correlation with altered sensitivity to glucose transport and antilipolysis to insulin[J]. J Clini Endocrin Metab,1988, Vol 66, 992-999.
[31] GerasimosP,Sykiotis,AthanasiosG.etal. Serine Phosphorylation of Insulin Receptor Substrate-1: ANovel Target for the Reversal of Insulin Resistance [J].Molecular Endocrinology, 2001, 15(11): 1864-1869.
[32] Beauloye C,Bertrand L,Krause U,etal. No-FlowIschemia Inhibits Insulin Signaling in Heart by Decreasing Intracellular pH[J]. Circulation Research. 2001;88:513.
[33] Tappy L, Randin D,Vollenweider P,et al. Mechanisms of dexamethasone-induced insulinresistance in healthy humans[J]. J.Clin. Endocrinol. Metab., 1994,79:1063-1069.
[34] Qi C,Pekala PH. Tumor necrosis factor-alpha-induced insulin resistance in adipocytes[J]. Proc-Soc-Exp-Biol-Med. 2000Feb; 223(2): 128-35 .
[35] Raticliffe JM,thorac cardiovasc surgenon ,1988;36:65.
[36] Uchtenberg RC ,J lab Clin Med ,1993;121-697.
[37] wasserman K , circulation ,1989;80;1084.
[38] Roytblat, L,Rachinsky, M, Fisher, A,et al Raised Interleukin-6 Levels in Obese Patients. Obes Res. 2000;8:673–675.
[39] Straczkowski, M,Dzienis-Straczkowska, S, Stepien, A,et al, Plasma Interleukin-8 Concentrations Are Increased in Obese Subjects and Related to Fat Mass and Tumor Necrosis Factor-{alpha} System. J Clin Endocrinol Metab. 2002;87:4602–4606.
[40] Hotamisligil, GS, Spiegelman, BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes. 1994;43:1271–1278.
[41] Sartipy, P, Loskutoff, DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. PNAS. 2003;100:7265–7270.
[42] Hotamisligil, GS, Arner, P, Caro, JF,et al Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[43] Visser, M, Bouter, LM,McQuillan, GM,et al ,Elevated C-Reactive Protein Levels in Overweight and Obese Adults. JAMA. 1999;282:2131–2135.
[44] Van Snick J.Interleukin-6: an overview. Annu Rev Immunol 1990;8:253-78.
[45]Fong Y,Moldawer LL,Marano M,etal.Endotoxemia elicits increased circulating B2-IFN/IL-6 in man. J Immunol1989;142: 2321-4.
[46] Zhang Y,Lin J-X,Yip YK,Vilcek J.Stimulation of Interleukin-6 mRNA levels by tumor necrosis factor and interleukin-1.Ann N Y Acad Sci 1989;557:548-9.
[47] Pullicino EA,Carli F,Poole S,etal.The relationship between the circulatingconcentrations of interleukin-6(IL6),tumor necrosis factor(TNF)and the acute phase response to elective surgery and accidental injury.Lymph Res 1990;9:231-8.
[48] Coceani F,Lees J,Mantilla J,etal.Interleukind and tumor necrosis factor in cerebrospinal fluid: changes during pyrogen fever.Brain Res 1993:612:165-71.
[49] Hennein HA,Ebba H,Rodriguez JL,etal.Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularisation.J Thorac Cardiovasc Surg 1994;108:626-35.
[50] Finkel MS,Oddis CV,Jacob TD,etal.Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992;257:387-9.
[51] Finkel MS.Hoffman RA.Shen L.etal.Interleukin-6(IL-6) as a mediator of stunned myocardium. Am J Cardiol 1993;71: 1231-2.
[52] Matsushima K,Taguchi M,Kovacs EJ,etal.Intracellular localization of human monocyte associated interleukin-1(IL-1)activity and release of biologically active IL-1 from monocytes by trypsin and plasmin.J Immunol 1986;136:2883-91.
[53]Tabardel Y,Duchateau J,Schmartz D,etal.Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men. Surgery 1996;119:76-80.
[54]Martinez-Pellus AE,Merino I’,Bru M,etal.Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by the cardiopulmonary bypass? Crit Care Med 1993;21:1684-91.
[55]Butler J,Baigrie RJ,Parker D,etal. Systemic inflammatory responses to cardiopulmonary bypass: a pilot study of the effects of pentoxifylline. Respir Med 1993;87:285-8.
[56] Markewitz A,Faist E,Lang S,etal.Regulation of acute phase response after cardiopulmonary bypass by immunomodulation. Ann Thorac Surg 1993;55:389-94.
[57] Markewitz A,Faist E,Lang S,etal.Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation. J Thorac Cardiovasc Surg 1993;105: 15-24.
[58] Markewitz A, Faist E,Weir&old C,etal. Alterations of cell mediated immune response following cardiac surgery. Eur J Cardiothorac Surg 1993;7:193-9.
[59] Menasche I’,Haydar S,Peynet J,etal. A potential mechanism of vasodilation after warm heart surgery: the temperature dependent release of cytokines. J Thorac Cardiovasc Surg 1994; 107293-9.
[60]Ohata T,Sawa Y,Kadoba K,etal.Normothermia has beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions. ASAIO J 1995;41:M288-91.
[61]Sawa Y,Shimazaki Y,Kadoba K,etal.Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations. J Thorac Cardiovasc Surg 1996;111:29-35.
[62]Hill GE,Snider S,Galbraith TA,etal.Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass.Am J Respir Crit Care Med 1995;152:1791-5.
[63] Kawamura T,Inada K,Okada H,etal. Methylprednisolone inhibits increase of interleukin8 and 6 during open heart surgery. Can J Anaesth 1995;42:399-403.
[64] Kawamura T,Inada K,Akasaka N,Wakusawa R.Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery.Can J Anaesth 1996;43:456-60.
[65] Millar AB,Armstrong L,van der Linden J,etal. Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass.Ann Thorac Surg 1993;56:1499-502.
[66] Joumois D,Pouard I’,Greeley WJ, etal. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery: effects on hemostasis,cytokines,and complement components. Anes- thesiology 1994;81:1181-9.
[67]Joumois D,Pouard I’,Rolland B, Lagarde M.Ultrafiltration allows to reduce cytokine plasma concentrations during pediatric cardiopulmonary bypass.Contrib Nephrol1995;116:86-8.
[68] Johnson D,Thomson D,Mycyk T,etal.Depletion of neutrophils by filter duringaortocoronary bypass surgery transiently improves postoperative cardiorespiratory status. Chest 1995; 1071253-9.
[69]Wang Ming J,Chiu IS,Hsu CM,etal.Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations.Ann Thorac Surg 1996;61:651-6.
[70]Butler J,Chong GL,Baigrie RJ,etal.Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 1992;53:833-8.
[71]Weerwind PW,Maessen JG,van Tits LJH,et al.Influence of Duraflo II heparin-treated extracorporeal circuits on the systemic inflammatory response in patients having coronary bypass. J Thorac Cardiovasc Surg 1995;110:1633-41.
[72] Gullestad L,Aukrust P,The cytokine network in heart failure ;pathgenetic importance and potential theurapeutic target[J] heart failure monit ,2001,2(1):8-13
[73] Senn JJ,KloverPJ, Nowak IA,et al. Interleukin induces cellular insulin resistance in hepatocytes.Diabetes, 2002, 51: 3391-9.
[74] Kopp, HP, et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003;23:1042–7.
[75] Fontana, L, Eagon, JC, Trujillo, ME, etal,Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010–3.
[76] Klover, PJ, Clementi, AH,Mooney, RA. Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology. 2005;146:3417–27.
[77]Wallenius V,Interleukin-6-deficient mice develop mature-onset obesity.Nat Med. 2002;8:75–9.
[78] Di Gregorio, GB, Hensley, L, Lu, T,et al. Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am J Physiol Endocrinol Metab. 2004;287:E182–7.
[79] Flier, JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell. 2004;116:337–50.
[80] Wernstedt I, Edgley A,Berndtsson A,etal, Reduced stress and coldinduced increase in energy expenditure in interleukin-6-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2006;291:R551–7.
[81] Yoshimura T,Matsushima K,Oppenheim JJ,etal.Neutrophil chemotactic factor produced by lipopolysaccharide(LPS)stimulated human blood mononuclear leukocytes:partial characterization and separation from interleukin1(IL -1). J Immunol 1987;139:788-93.
[82] Thelen M,Peveri P,Kernen I’,etal.Mechanism of neutrophil activation by NAF,a novel monocyte derived peptide agonist. FASEB J 1988;2:2702-6.
[83] Huber A,Kunkel SL,Todd RF III,etal.Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science 1991;254:99-102.
[84] Colditz IG,Zwahlen RD,Baggiolini M.Neutrophil accumulation and plasma leakage induced in vivo by neutrophil activating peptide1. J Leuk Biol 1990;48:129-37.
[85] Inaba H,Kochi A,Yorozu S.Suppression by methylprednisolone of augmented plasma endotoxin like activity and interleukin-6 during cardiopulmonary bypass.Br J Anaesth 1994; 72:348-50.
[86] Engelman RM,Rousou JA,Flack JE III,etal.Influence of steroids on complement and cytokine generation after cardiopulmonary bypass.AM Thorac Surg 1995;60:801-4.
[87] Finn A,Naik S,Klein N,etal.Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;105:234-41.
[88] Kawamura T,Wakusawa R,Okada K,Inada S.Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin8 and 6 in reperfusion injury. Can J Anaesth 1993;40:1016-21.
[89] Finn A,Moat N,Rebuck N,etal.Changes in neutrophil CDllb/CD18 and I-selectin expression and release of interleukin 8 and elastase in paediatric cardiopulmonary bypass.Agents Actions 1993;38:C44-6.
[90] Jorens PG,de Jongh R,de Backer W,etal.Interleukin-8 production in patients undergoing cardiopulmonary bypass:the influence of pretreatment with methylprednisolone. Am Rev Respir Dis 1993;148:890-5.
[91]Sheron N,Williams R.IL-8 as a circulating cytokine:induction by recombinant tumour necrosis factor-alpha. Clin Exp Immuno1 1992;89:100-3.
[92]Tiinz M,Mihaljevic T,von Segesser LK,etal.Acute lung injury during cardiopulmonary bypass: are the neutrophils responsible? Chest 1995;108:1551-6.
[93] Burns SA,Newburger JW,Xiao M,et al.Induction of interleukin-8 messenger RNA in heart and skeletal muscle during pediatric cardiopulmonary bypass.Circulation 1995; 92(Suppl 11):315-21.
[94] El Habbal MH,Carter H,Smith LJ,etal.Neutrophil activation in paediatric extracorporeal circuits:effect of circulation and temperature variation.Cardiovasc Res 1995;29:102-7.
[95]McBride WT,Armstrong MA,Crockard AD,etal.Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. Br J Anaesth 1995;75:724-33.
[96]de Waal Malefyt R,Abrams J,Bennett B,et al.Interleukin-10(IL-l0) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991;174:1209-20.
[97]Chernoff AE, Granowitz EV,Shapiro L,etal.A randomized,controlled trial of IL-10 in humans. J Immunol1995;154:5492-9.
[98] Seghaye Marie-C,Duchateau J,Bruniaux J,etal.Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg 1996;lll:
[99] Stefano GB,Rodriguez M,Glass R, etal.Hyperstimulation of leukocytes by plasma fromcardiopulmonary bypass patients is diminished by morphine and IL-10 pretreatment.J Cardio- vast Surg 1995;36:25-30.
[100] Shottelius A., Mayo M.W., Sartor R.B.,etal. Interleukin-10 signaling blocks inhibitor of kB kinase activity and nuclear factor kB DNA binding. J Biol Chem 1999;274:31868-31874.
[101] van Exel E, Gussekloo J, de Craen AJ,et al .Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study. Diabetes. 2002;51:1088–92.
[102] Kim HJ, Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes. 2004;53:1060–7.
[103] Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175–84.
[104] Hotamisligil GS,Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
[105] Hotamisligil GS, Arner P, Caro JF,etal. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[106] Hotamisligil GS,Peraldi P, Budavari A,etal. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.
[107] Uysal KT, Wiesbrock SM, Marino MW,etal. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610–4.
[108] Stephens JM, Lee J,Pilch PF. Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem. 1997;272:971–6.
[109] Ruan H, Hacohen N,Golub TR,etal.Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes. 2002;51:1319–36.
[110] Leinonen E, Hurt-Camejo E,W iklund O,et al. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesionmolecules in type2 diabetes. Atherosclerosis, 2003, 166:387-94.
[111]The Systemic Inflammatory Response to Cardiopulmonary Bypass: Pathophysiological,Therapeutic,and Pharmacological Considerations[J]Anesth Analg 1997;85:766-782
[112]张拥军,肖诗亮,聂荣华,等.肿瘤坏死因子-α与体外循环中胰岛素抵抗的研究[J]临床外科杂志,2007,4,15(4):261-263.
[113] KirklinJK.ProsPect for understanding and eliminating the deleterious effects of cardiopulmonary bypass .[J]Ann thorac surg 1991;51:529-531
[114]Engellman DT,MD,Wantanable M,MD,Manlik,N,PhD,etal.L-Arginine reduces endothelial inflammation and myocardial stunning ischemia reperfusion.[J] AnnThoracsurg1995:60:1275-1281.
[115] Angele MK,MD,Smai1 N,MD,Ayala A,PhD,et al.L-Arginine:a unique amino acid for restoring the depressed macrophage funetions after trauma-hemorrhage.[J] Trauma. 1999 Jan;46(1):34-41.
[116]Clermont G,Vergely C,Cellular injury associated with extracorporeal circulation.[J]AnnCardiolAngeiol2002:51:38一43.
[117] Barbul, B. Arginine: biochemistry, physiology, and therapeutic implications.[J] Parenter Enteral Nutr. 1986;10:227–238.
[118] Wu, G,Morris,SM., Jr Arginine metabolism: nitric oxide and beyond. [J]Biochem J. 1998;336:1–17.
[119] Palmer RMJ,Ashton AS,Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine.[J] Nature. 1998;333:664–666.
[120] Loscalzo J, Welch G. Nitric oxide and its role in the cardiovascular system. [J]Prog Cardiovasc Dis. 1995;35:87–104.
[121] Durante W. Regulation of L-arginine transport and metabolism in vascular smooth muscle cells.[J] Cell Biochem Biophys. 2001;35:19–34.
[122] John S, Schmeider RE. Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia.[J] Curr Hypertens Rep. 2003;5:199–207.
[123] Soriano FG, Virag L, Szabo C. Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation. [J] Mol Med. 2001;79:437–448.
[124] Lefer Am, Lefer DJ.The role of nitric oxide and cell adhesion molecules on the microcirculation in ischemia-reperfusion.[J] Cardiovas Res. 1996;32:743–751.
[125] Drexler H, Zeiher AM, Meinzer K,etal.Correction of endothelial dysfunction in coronary microcirculation of hypercholestrolemic patients by L-arginine.[J] Lancet. 1991;67:1301–1308.
[126] Cooke JP, Singer AH, Tsao P,etal, Antiatherogenic effects of L-arginine in the hypercholestrolemic rabbit. [J ]Clin Invest. 1992;90:1168–1172.
[127] Tarry WC, Markhoul RG. L-Arginine improves endothelial-dependent vasorelaxation and reduces intimal hyperplasia after balloon injury.[J]ArteriosclerThromb. 1994;14:938–943.
[128] Loscalzo J.An experiment in nature: genetic L-arginine deficiency and NO insufficiency.[J] Clin Invest. 2001;108:663–664.
[129]刘庆.L-精氨酸对胰岛素抵抗大鼠血压及胰岛素抵抗[D]天津医科大学.2004
[130] Moncada S, Palmer RMJ, Higgs EA. Nitric oxide:physiology,pathophysiology, and pharmacology.[J] Pharmacol Rev, 1991, 43
[131] Furchgott RF,Carvaho MH.Evidence for endothelium-dependent vasodilation ofresistance vessels by acetylcholing.[J]Blood Vessels,1987,24(3):145-149.;1991, 43(2):109-142.;
[132] Furlong B, Henderson AM, Lewis MJ,etal. Endothelium-derived relaxing factor inhibits in vitro platelet. [J]Br J Pharmacol,1987, 90(4):687-692.
[133] Kubes P, Suzuki M, Granger DN. Nitric oxide:an endogenousmodulator of leukocyte adhesion. [J]Proc Natl Acad Sci USA,1991, 88(11):4651-4655,
[134] Rakoff JS, Sile JM, Sinha YN,et al. Prolactin and grouthhormone release in respomse to sequential stimulation by arginineand TRF.[J]Clin Eedocrinol Metab, 1973, 37(4):641-644.。
[135] Angele MK,MD,Smai1 N,MD,Ayala A,PhD,etal.L-Arginine:a unique amino acid for restoring the depressed macrophage functions after trauma hemorrhage.[J] Trauma1999:46(1):34-39.
[136] CendanJC,MD,Souba WW,MD,ScD,Edward M,etal.Cytokines regulate endotoxin stimulation of endothelial cell arginine transPort.[J]Surg1995;117:213-219.
[1] Thoerll A,Nygrne J,Essen P,et al. The metabolic response to cholecystectomy: insulin Resistance after open compared with laparoscopic operation.Eur J Surg.1996Mar;162(3):187一91.
[2]《体外循环学》,龙村主编,人民军医出版社,2004,1-17.
[3]SwanJW,WaltonC,GdeslandIF,Insulin resistance in chronic heart failure[J].EurHeartJ.1994,15(11):1528-32.
[4] Swna JW,Anker SD,Walton C,et al. Insulin resistance in chronic heart failure: Relation to severity and etiology of heart failure[J].JAmcollCardiol,1997,30(2):527-32.
[5] Clement K,Genetic variation in the beta 3-adrenergic receptor and Increased capacity to gain weight in Patients with morbid obesity[J].Nengl J Med,1995,333(6):352-4.
[6]李光伟,潘效仁,LinoijaS等.检测人群胰岛素抵抗的一项新指数[J].中华内科杂,1993,32(11):656-660.
[7]罗宗,秦文勇,胰岛素抵抗与充血性心力衰竭关系的研究[J]西藏科技.2009:2:51-52
[8] Giroir BP. Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade. Crit Care Med 1993;21:780-9.
[9] Blick M,Sherwin SA,Rosenblum M,et al .Phase I study of recombinant tumor necrosis factor in cancer patients. Cancer Res 1987;47:2986-9.
[10] Smith JW II,Urba WJ,Curti B,et al.The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies. J Clin Oncol 1992;l0: 1141-52.
[11] Kaushansky K,Broudy VC,Harlan JM,et al.Tumor necrosis factor and tumor necrosis factor-p (Lymphotoxin) stimulate the production of granulocyte-macrophage colony stimulating factor,macrophage colony stimulating factor,and IL-1 in vivo. J Immunol 1988;141:3410-5.
[12] Zhang Y, Lin J-X,Yip YK,et al. Stimulation of Interleukin-6 mRNA levels by tumor necrosis factor and interleukin-1. Ann N Y Acad Sci 1989;557:548-9.
[13] Matsushima K,Taguchi M,Kovacs EJ,et al.Intracellular localization of human monocyte associated interleukin 1 (IL-1) activity and release of biologically active IL-1 from monocytes by trypsin and plasmin. J Immunol 1986;136:2883-91.
[14] Inaba H,Kochi A,Yorozu S.Suppression by methylprednisolone of augmented plasma endotoxin like activity and interleukin-6 during cardiopulmonary bypass.Br J Anaesth 1994; 72:348-50.
[15] Engelman RM, Rousou JA,Flack JE III,et al. Influence of steroids on complement and cytokine generation after cardiopulmonary bypass. AM Thorac Surg 1995;60:801-4.
[16] Tabardel Y,Duchateau J,Schmartz D,et al.Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men. Surgery 1996;119:76-80.
[17] Martinez-Pellus AE,Merino I’,Bru M,et al.Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by the cardiopulmonary bypass? Crit Care Med 1993;21:1684-91.
[18] Butler J,Baigrie RJ,Parker D,etal.Systemic inflammatory responses to cardiopulmonary bypass:a pilot study of the effects of pentoxifylline. Respir Med 1993;87:285-8.
[19] Markewitz A,Faist E, Lang S, et al.Regulation of acute phase response after cardiopulmonary bypass by immunomodulation. Ann Thorac Surg 1993;55:389-94.
[20] Markewitz A,Faist E,Lang S,etal.Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation.J Thorac Cardiovasc Surg 1993;105: 15-24.
[21] Markewitz A,Faist E, Weir&old C,et al.Alterations of cell mediated immune response following cardiac surgery. Eur J Cardiothorac Surg 1993;7:193-9.
[22] Menasche I’,Haydar S,Peynet J,et al.A potential mechanism of vasodilation after warmheart surgery:the temperature dependent release of cytokines.J Thorac Cardiovasc Surg 1994; 107293-9.
[23] Ohata T,Sawa Y,Kadoba K,et al.Normothermia has beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions. ASAIO J 1995;41:M288-91.
[24] Murray DRFreeman GL.Tumor necrosis factor-alpha induces a biphasic effect on myocardial contractility in conscious dogs[J].Cier Res,1996,78(l):154一160.
[25] Lee RE,Lotze MT,Skibber JM,et al.Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol 1989;7:7-20.
[26] Fujiwara T,Grimm EA.Specific inhibition of interleukin 1B gene expression by an antisense oligonucleotide:obligatory role of interleukin-1 in the generation of lymphokine activated killer cells. Cancer Res 1992;52:4954-9.
[27] Giovarelli M,Santoni A,Jemma C,et al.Obligatory role of IFN-y in induction of lymphokine-activated and T lymphocyte killer activity,but not in boosting of natural cytotoxicity.J Immunol 1988;141:2831-6.
[28] Van Snick J.Interleukin-6:an overview. Annu Rev Immunol 1990;8:253-78.
[29] Fong Y,Moldawer LL,Marano M,et al.Endotoxemia elicits increased circulating B2-IFN/IL-6 in man.J Immunol 1989;142: 2321-4.
[30] Hennein HA,Ebba H,Rodriguez JL,et al.Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularisation. J Thorac Cardiovasc Surg 1994;108:626-35.
[31] Finkel MS,Oddis CV,Jacob TD,et al.Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992;257:387-9.
[32] Coceani F,Lees J,Mantilla J,et al.Interleukind and tumor necrosis factor in cerebrospinal fluid: changes during pyrogen fever. Brain Res 1993:612:165-71.
[33] Pullicino EA,Carli F,Poole S,et al.The relationship between the circulating concentrations of interleukin-6(IL6),tumor necrosis factor(TNF) and the acute phaseresponse to elective surgery and accidental injury.Lymph Res 1990;9:231-8.
[34] Finkel MS.Hoffman RA.Shen L.et al.Interleukin-6(IL-6) as a mediator of stunned myocardium. Am J Cardiol 1993;71: 1231-2.
[35] Sawa Y,Shimazaki Y,Kadoba K,etal.Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations.J Thorac Cardiovasc Surg 1996;111:29-35.
[36] Hill GE,Snider S,Galbraith TA,etal.Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass.Am J Respir Crit Care Med 1995;152:1791-5.
[37] Kawamura T,Inada K,Okada H,et al.Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery. Can J Anaesth 1995;42:399-403.
[38] Kawamura T,Inada K,Akasaka N,Wakusawa R.Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery.Can JAnaesth 1996;43:456-60.
[39] Millar AB,Armstrong L,van der Linden J,etal.Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass. Ann Thorac Surg 1993;56:1499-502.
[40] Joumois D,Pouard I’,Greeley WJ,etal. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery:effects on hemostasis,cytokines, and complement components. Anesthesiology 1994;81:1181-9.
[41] Joumois D,Pouard I’, Rolland B,Lagarde M.Ultrafiltration allows to reduce cytokine plasma concentrations during pediatric cardiopulmonary bypass.Contrib Nephrol1995;116:86-8.
[42] Johnson D,Thomson D,Mycyk T,etal.Depletion of neutrophils by filter during aortocoronary bypass surgery transiently improves postoperative cardiorespiratory status. Chest 1995; 1071253-9.
[43] Wang Ming J,Chiu IS,Hsu CM,etal.Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations.Ann Thorac Surg 1996;61:651-6.
[44] Butler J,Chong GL,Baigrie RJ,etal.Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 1992;53:833-8.
[45] Weerwind PW,Maessen JG,van Tits LJH,etal.Influence of Duraflo II heparin-treated extracorporeal circuits on the systemic inflammatory response in patients having coronary bypass. J Thorac Cardiovasc Surg 1995;110:1633-41.
[46] Yoshimura T,Matsushima K,Oppenheim JJ,Leonard EJ.Neutrophil chemotactic factor produced by lipopolysaccharide(LPS) stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin-1(IL-1).JImmunol 1987;139:788-93.
[47] Thelen M,Peveri P,Kernen I’,etal.Mechanism of neutrophil activation by NAF,a novel monocyte derived peptide agonist.FASEB J 1988;2:2702-6.
[48] Huber A,Kunkel SL,Todd RF III,etal.Regulation of transendothelial neutrophil migration by endogenous interleukin-8.Science 1991;254:99-102.
[49] Colditz IG,Zwahlen RD,Baggiolini M.Neutrophil accumulation and plasma leakage induced in vivo by neutrophil activating peptide-1.J Leuk Biol 1990;48:129-37.
[50] Jorens PG,de Jongh R,de Backer W,et al.Interleukin-8 production in patients undergoing cardiopulmonary bypass:the influence of pretreatment with methylprednisolone.Am Rev Respir Dis 1993;148:890-5.
[51] Finn A,Naik S,Klein N,etal.Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;105:234-41.
[52] Kawamura T,Wakusawa R,Okada K,Inada S.Elevation of cytokines during open heart surgery with cardiopulmonary bypass:participation of interleukin-8 and 6 in reperfusion injury. Can J Anaesth 1993;40:1016-21.
[53] Finn A,Moat N,Rebuck N,etal.Changes in neutrophil CDllb/CD18 and I-selectin expression and release of interleukin-8 and elastase in paediatric cardiopulmonary bypass. Agents Actions 993;38:C44-6.
[54] Sheron N,Williams R.IL-8 as a circulating cytokine:induction by recombinant tumournecrosis factor-alpha. Clin Exp Immuno1 1992;89:100-3.
[55] Tiinz M,Mihaljevic T von Segesser LK,etal.Acute lung injury during cardiopulmonary bypass:are the neutrophils responsible? Chest 1995;108:1551-6.
[56] Burns SA,Newburger JW,Xiao M,etal.Induction of interleukin-8 messenger RNA in heart and skeletal muscle during pediatric cardiopulmonary bypass.Circulation 1995; 92(Suppl 11):315-21.
[57] El Habbal MH,Carter H, Smith LJ,etal.Neutrophil activation in paediatric extracorporeal circuits:effect of circulation and temperature variation.Cardiovasc Res 1995;29:102-7.
[58] Kharazmi A,Andersen LW,Baek L,etal.Endotoxemia and enhanced generation of oxygen radicals by neutrophils from patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989;98:381-5.
[59] cavarocchi NC,England MD,Schaff HV,etal.Oxygen free radical generation during cardiopulmonary bypass:correlation with complement activation. Circulation 1986;74(Suppl III): 130-3.
[60] Sinclair DG, Haslam PL,Quinlan GJ,etal.The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability.Chest 1995;108:718-24.
[61] Davies SW,Underwood SM,Wickens DG,etal.Systemic pattern of free radical generation during coronary bypass surgery.Br Heart J 1990;64:236-40.
[62] Schorer AE,Moldow CF,Rick ME.Interleukin-1 or endotoxin increases the release of von Willebrand factor from human endothelial cells.Br J Haematol 1987;67:193-7.
[63] Elliott MJ,Finn AHR.Interaction between neutrophils and endothelium.Ann Thorac Surg 1993;56:1503-8.
[64] Fosse E,Mollnes TE,Osterud A,etal.Effects of methylprednisolone on complement activation and leukocyte counts during cardiopulmonary bypass.Stand J Thorac Cardiovasc Surg 1987;21:255-61.
[65] Jansen NJG,van Oeveren W, Broek Lvd, et al.Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass.J Thorac Cardiovasc Surg 1991;102:515-25.
[66] van Oeveren W,Jansen NJG,Bidstrup BP,etal.Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass.Ann Thorac Surg 1987;44:640-5.
[67]Taggart DP,Sundaram S,McCartney C,etal.Endotoxemia,complement,and white blood cell activation in cardiacsurgery:a randomized trial of laxatives and pulsatile perfusion.Ann Thorac Surg 1994;57:376-82.
[68] Jansen PGM,Te Velthuis H,Wildevuur WR,etal.Cardiopulmonary bypass with modified gelatin and heparin coated circuits.Br J Anaesth 1996;76:13-9.
[69] Dapper F,Neppl H,Wozniak G,etal.Influence of 4 different membrane oxygenators on inflammation like processes during extracorporeal circulation with pulsatile and non-pulsatile flow.Eur J Cardiothorac Surg 1992;6:18-24.
[70] Driessen JJ,Dhaese H,Fransen G,etal.Pulsatile compared with nonpulsatile perfusion using a centrifugal pump for cardiopulmonary bypass during coronary bypass grafting: effects on systemic haemodynamics,oxygenation,and inflammatory response parameters. Perfusion 1995;10:3-12.
[71]Nilsson L,Nilsson U,Venge I’,etal.Inflammatory system activation during cardiopulmonary bypass as an indicator of biocompatibility: a randomized comparison of bubble and membrane oxygenators. Stand J Thorac Cardiovasc Surg 1990; 24:53-8.
[72] Nilsson L,Tyden H,Johansson o,etal.Bubble and membrane oxygenators:comparison of postoperative organ dysfunction with special reference to inflammatory activity.Stand J Thorac Cardiovasc Surg 1990;24:59-64.
[73] Gillinov AM,Bator JM,Zehr KJ,etal.Neutrophil adhesion molecule expression during cardiopulmonary bypass with bubble and membrane oxygenators.Ann Thorac Surg 1993;56: 847-53.
[74]Gu YJ,van Oeveren W,Akkerman C,etal.Heparin coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:917-22.
[75] Fosse E,Moen 0,Johnson E,etal.Reduced complement and granulocyte activation with heparin coated cardiopulmonary bypass.Ann Thorac Surg 1994;58:472-7.
[76] Hatori N,Yoshizu H,Haga Y,etal.Biocompatibility of heparin coated membrane oxygenator during cardiopulmonary bypass.Artif Organs 1991;18:904-10.
[77] Pekna M,Borowiec J,Fagerhol MK,etal.Biocompatibility of heparin coated circuits used in cardiopulmonary bypass. Stand J Thorac Cardiovasc Surg 1994;28:5-11.
[78]McBride WT,Armstrong MA,Crockard AD,etal.Cytokine balance and immunosuppressive changes at cardiac surgery:contrasting response between patients and isolated CPB circuits.Br J Anaesth 1995;75:724-33.
[79] De Waal Malefyt R,Abrams J,Bennett B,etal.Interleukin-10 (IL-l0)inhibits cytokine synthesis by human monocytes:an autoregulatory role of IL-10 produced by monocytes.J Exp Med 1991;174:1209-20.
[80] Chernoff AE,Granowitz EV,Shapiro L,etal.A randomized, controlled trial of IL-10 in humans.J Immunol1995;154:5492-9.
[81] Seghaye Marie C,Duchateau J,Bruniaux J,etal.Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg 1996;lll:
[82] Stefano GB, Rodriguez M,Glass R,etal.Hyperstimulation of leukocytes by plasma from cardiopulmonary bypass patients is diminished by morphine and IL-10 pretreatment.J Cardio- vast Surg 1995;36:25-30.
[83] Shottelius A,Mayo M.W.,Sartor R.B.,et al. Jr Interleukin-10 signaling blocks inhibitor of kB kinase activity and nuclear factor kB DNA binding. J Biol Chem 1999;274:31868-31874.
[84] D.Paparellaa*,T.M. Yaua, E. Youngb ,et al .Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update Eur J Cardiothorac Surg 2002;21:232-244.
[85] Chenoweth D.E.,Cooper S.W.,Hugli T.E.,etal.BlackstoneE.H., Kirklin J.W.Complement activation during cardiopulmonary bypass:evidence for generation of C3a and C5a anaphylotoxins. N Engl J Med 1981;304:497-503.
[86] Bruins P.,te Velthuis H.,Yazdanbakhsh A.P.,etal.Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation 1997;96:3542-3548.
[87] Gu J.Y.,Mariani M.A.,Boonstra P.W.,etal.Complement activation in coronary artery bypass grafting patients without cardiopulmonary bypass. Chest 1999;116:892-898.
[88] Kyriakides C.,Wang Y.,Austen W.G,etal.Moderation of skeletal muscle reperfusion injury by a sLex-glycosylated complement inhibitory protein.Am J Physiol Cell Physiol 2001;281:C224-C230.
[89] Giroir B.P. Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade. Crit Care Med 1993;21:780-789.
[90] Jirik F.R., Podor T.J., Hirano T.,etal.Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol 1989;142:144-147.
[91] Andersen L.W.,Landow L.,Baek L.,etal. Association between gastric intramucosal ph and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor- concentration in patients undergoing cardiopulmonary bypass. Crit Care Med 1993;21:210-217.
[92]Riddington D.W.,Venkatesh B.,Boivin C.M.,etal.Intestinal permeability,gastric intramucosal ph, and systemic endotoxemia in patients undergoing cardiopulmonary bypass. J Am Med Assoc 1996;275:1007-1012.
[93] Lequier L.L.,Nikaidoh H.,Leonard S.R.,et al.Preoperative and postoperative endotoxemia in children with congenital heart disease. Chest 2000;117:1706-1712.
[94] Busse R,Mulsch A.Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett 1990;275: 87-90.
[95] Petros A,Bennett D,Valiance I’.Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock.Lancet 1991;338:1557-8.
[96] Kubes I’,Suzuki M,Granger DN.Nitric oxide:an endogenous modulator of leukocyte adhesion.Proc Nat1 Acad Sci USA 1991;88:4651-5.
[97]Moncada I,Higgs A.The L-arginine-nitric oxide pathway.N Engl J Med 1993;329:2002-12.
[98] Matheis G,Sherman Ml’,Buckberg GD,etal.Role of L-arginine-nitric oxide pathway in myocardial reoxygenation iniury. Am 1 Phvsiol 1992:262:H616-20.
[99] Delgado R,*Rojas A,Glaria LA,etal.Ca’+-independent nitric oxide synthase activity in human lung after cardiopulmonary bypass.Thorax 1995;50:403-4.
[100] Moncada S.,Higgs A.Mechanisms of disease: the L-arginin-nitric oxide pathway. N Engl J Med 1993;329:2002-2012.
[101] Worrall N.K., Chang K., Lejeunne W.S.,etal.TNF- causes reversible in vivo systemic vascular barrier dysfunction via NO-dependent and -independent mechanisms. Am J Physiol 1997;273:H2565-H2574.
[102] Oyama J.,Shimokawa H.,Momii H.,et al.Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo.J Clin Invest 1998;101:2207-2214.
[103] Sato H.,Zhao Z.Q.,Todd J.C.,etal.Basal nitric oxide expresses endogenous cardioprotection during reperfusion by inhibition of neutrophil-mediated damage after surgical revascularization. J Thorac Cardiovasc Surg 1997;113:399-409.
[104] Engelman D.T.,Watanabe M.,Engelman R.M.,etal.Constitutive nitric oxide release is impaired after ischemia and reperfusion. J Thorac Cardiovasc Surg 1995;110:1047-1053.
[105] Christman J.W.,Lancaster L.H.,Blackwell T.S. Nuclear factor k B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med 1998;24:1131-1138.
[106] Baldwin A.S.,Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996;14:649-683.
[107] Li C.,Browder W.,Kao R.L.Early activation of transcription factor NF-kB during ischemia in perfused heart rat. Am J Physiol 1999:H543-H552.
[108] Oitzinger W.,Hofer-Warbinek R.,Schmid J.A.,etal. Adenovirus-mediated expression of a mutant IkB kinase 2 inhibits the response of endothelial cells to inflammatory stimuli. Blood 2001;97:1611-1617.
[109] Ilton M.K.,Langton P.E.,Taylor M.L.,etal.Differential expression of neutrophil adhesion molecules during coronary artery surgery with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1999;118:930-937.
[110] Jordan J.E.,Zhao Z.Q.,Vinten-Johansen J.The role of neutrophils in myocardial ischemia–reperfusion injury. Cardiovasc Res 1999;43:860-878.
[111] Zahler S.,Massoudy P.,Hartl H.,etal.Acute cardiac inflammatory response to postischemic reperfusion during cardiopulmonary bypass. Cardiovasc Res 1999;41:722-730.
[112] Wahba A.,Rothe G.,Lodes H.,etal.Effects of extracorporeal circulation and heparin on the phenotype of platelet surface antigens following heart surgery.Thromb Res 2000;97:379-386.
[113] Roytblat L,Rachinsky, M,Fisher A,etal.Raised Interleukin-6 Levels in Obese Patients. Obes Res. 2000;8:673–675.
[114] Straczkowski M,Dzienis-Straczkowska S,Stepien A,etal.Plasma Interleukin-8 Concentrations Are Increased in Obese Subjects and Related to Fat Mass and Tumor Necrosis Factor-{alpha} System. J Clin Endocrinol Metab. 2002;87:4602–4606.
[115] Hotamisligil GS, Spiegelman BM.Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes. 1994;43:1271–1278.
[116] Sartipy P,Loskutoff DJ.Monocyte chemoattractant protein 1 in obesity and insulin resistance. PNAS. 2003;100:7265–7270.
[117] Hotamisligil GS,Arner P,Caro JF,etal.Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[118]Visser M,Bouter LM,McQuillan GM,etal.Elevated C-Reactive Protein Levels in Overweight and Obese Adults. JAMA. 1999;282:2131–2135.
[119] Leinonen E,Hurt-Camejo E,W iklund O,etal. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesionmolecules in type 2 diabetes. Atherosclerosis, 2003, 166:387-94.
[120] Cone RD.Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8:571–8.
[121] de Luca C,Olefsky JM.Stressed out about obesity and insulin resistance. Nat Med. 2006;12:41–2. discussion 42.
[122] Yu C,Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem. 2002;277:50230–6.
[123] Pickersgill L,Litherland GJ, Greenberg AS,etal.Key role for ceramides in mediating insulin resistance in human muscle cells. J Biol Chem. 2007
[124] Lee JS, Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol. 2006;100:1467–74.
[125] Taniguchi CM,Emanuelli B,Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol. 2006;7:85–96.
[126] Aguirre V,Werne ED Giraud J,etal.Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action. J Biol Chem. 2002;277:1531–1537.
[127]Rui L,Yuan M,Frantz D,etal.SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem. 2002;277:42394–8.
[128] Imamura T,G alpha-q/11 protein plays a key role in insulin-induced glucose transport in 3T3-L1 adipocytes. Mol Cell Biol. 1999;19:6765–74.
[129] Usui I,Imamura T, Huang J,etal. Cdc42 is a Rho GTPase family member that can mediate insulin signaling to glucose transport in 3T3-L1 adipocytes. J Biol Chem. 2003;278:13765–74.
[130] Baumann CA, CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature. 2000;407:202–7.
[131] Hotamisligil GS,Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
[132]Hotamisligil GS,Arner P,Caro JF,etal.Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[133] Hotamisligil GS,Peraldi P,Budavari A,etal.IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.
[134] Uysal KT,Wiesbrock SM,Marino MW,etal.Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610–4.
[135] Stephens JM,Lee J,Pilch PF. Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem. 1997;272:971–6.
[136] Ruan H,Hacohen N,Golub TR,etal.Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes. 2002;51:1319–36.
[137] Hotamisligil GS,Shargill NS,Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
[138] Dandona P,Weinstock R,Thusu K,etal. Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab. 1998;83:2907–10.
[139] Paz K,Hemi R,LeRoith Detal.A molecular basis for insulin resistance: elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation. J Biol Chem. 1997;272:29911–8.
[140] Aguirre V,Uchida T,Yenush L,etal. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000;275:9047–54.
[141] Yang R, Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese mice. J Biol Chem. 2007;282:22765–74.
[142] Tuncman G,Hirosumi J,Solinas G,etal. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci U S A. 2006;103:10741–6.
[143]Yuan M,Konstantopoulos N,Lee J,et al. Reversal of obesityand diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science. 2001;293:1673–7.
[144]Yin MJ,Yamamoto Y,Gaynor RB.The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature. 1998;396:77–80.
[145] Ebstein W.Zur Therapie des Diabetes mellitus, insbesondereüber die Anwendung des salicylsauren Natron bei demselben. Berliner Klinische Wochenschrift. 1876;13:337–40.
[146] Cai D,Yuan M,Frantz DF,etal.Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183–90.
[147] Arkan MC,etal.IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med. 2005;11:191–8.
[148] Williamson RT,Lond MD.On the treatment of glycosuria and diabetes mellitus with sodium salicylate. British Med J. 1901;1:760–762.
[149] Kim JK,etal.Prevention of fat-induced insulin resistance by salicylate. J Clin Invest. 2001;108:437–46.
[150]Sugita H,Fujimoto M,Yasukawa T,etal.Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem. 2005;280:14203–11.
[151] Yasukawa T,Tokunaga E,Ota H,etal.S-nitrosylation-dependent inactivation of Akt/protein kinase B in insulin resistance. J Biol Chem. 2005;280:7511–8.
[152] Perreault M,Marette A.Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med. 2001;7:1138–43.
[153] Carvalho-Filho MA,Ueno M,Carvalheira JB,etal.Targeted disruption of iNOS prevents LPS-induced S-nitrosation of IRbeta/IRS-1 and Akt and insulin resistance in muscle of mice. Am J Physiol Endocrinol Metab. 2006;291:E476–82.
[154]Carvalho-Filho MA, S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt:a novel mechanism of insulin resistance. Diabetes. 2005;54:959–67.
[155] Schottelius AJ,Mayo MW,Sartor RB,etal.Jr Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding.J Biol Chem. 1999;274:31868–74.
[156] van Exel E,Gussekloo J,de Craen AJ,etal.Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study. Diabetes. 2002;51:1088–92.
[157] Kim HJ, Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes. 2004;53:1060–7.
[158] Lumeng CN,Bodzin JL,Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175–84.
[159] Senn JJ,KloverPJ, Nowak IA,Interleukin induces cellular insulin resistance in hepatocytes.Diabetes, 2002, 51: 3391-9.
[160] Kopp HP, Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003;23:1042–7.
[161] Fontana L,Eagon JC,Trujillo ME,etal.Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010–3.
[162] Klover PJ,Clementi AH,Mooney RA.Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology. 2005;146:3417–27.
[163] Wallenius V,Interleukin-6-deficient mice develop mature-onset obesity.Nat Med. 2002;8:75–9.
[164] Di Gregorio GB,Hensley L, Lu T, etal.Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am J Physiol Endocrinol Metab. 2004;287:E182–7.
[165] Flier JS.Obesity wars: molecular progress confronts an expanding epidemic.Cell. 2004;116:337–50.
[166] Wernstedt I, Edgley A, Berndtsson A,etal. Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2006;291:R551–7.
[167] Febbraio MA.gp130 receptor ligands as potential therapeutic targets for obesity. J Clin Invest. 2007;117:841–9.
[168]Marina Cardellini MD.Lucia Perego PHD,Monica D’Adamo MD,etal.C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance.J Diabetes Care 28:2007-2012,2005.
[169] Dinarello, CA. Blocking IL-1 in systemic inflammation. J Exp Med. 2005;201:1355–9.
[170] Matsuki T,Horai R, Sudo K,etal.IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions. J Exp Med. 2003;198:877–88.
[171]Spranger J,Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003;52:812–7.
[172] Jager J,GremeauxT,Cormont M,Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007;148:241–51.
[173] Zerr KJ,Furnary AP,Grunkemeier GL,etal.Glucose Control Lowers the Risk of Wound Infection in Diabetics afterOpen-Heart Operation[J]. Ann Thorac Surg 1997,63:356-361.
[174] Rassias A,Marrin CAS,Arruda J,etal. Insulin Infusion Improves Neutrophil Function in Diabetic Cardiac Surgery Patients[J]. Anesth Analg. 1999,88:1011-1016.
[175] Rassias A,Givan A,Marrin CA S,etal.Insulin Increases Neutrophil Count and Phagocytic Capacity after Cardiac Surgery[J].Anesth Analg. 2002,94:1113-1119.
[176] Lazar HL,Chipkin S,Philippides G,etal. Glucose insulin-potassium solutions improve outcomes in diabetics who have coronary artery operations[J].Ann Thorac Surg. 2000,70:145-150.
[177] Ramanathan T,Shirota K,Morita S,etal. Glucose-insulin-potassium solution improves left ventricular mechanics in diabetes[J]. Ann Thorc Surg. 2002,73:582-587.
[178] Lell WA,Neilson VG,McGiffin,DC,etal.Glucose-insulin-potassium infusion for myocardial protection during off-pump coronary artery surgery[J].Ann Thorac Surg. 2002,73:1246-1251.
[179] Thorell A, Nygren J,Ljungqvist O,etal. Insulin resistance: a marker of surgical stress[J]. Curr Opin NutrMetab Care,1999, 2:69-78.
[180] Silistreli E,CatalyurekH,SariosmanoN,etal.Effectson the Endocrine System of Pulsatile and Nonpulsatile in Heart Surgery[J].Asian Cardiovasc Thorac Ann,1999,7:18-22.
[181]王占科,许霖水,吴贵喜.TNF-α与烧伤后胰岛素抵抗相关性的研究[J].第三军医大学学报,1997,19:310-312.
[182]Friehs I,Stamm C,Hung C D,et al. Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts[J].Ann Thorac Surg. 2001,72:1650-1656. .
[2]薛纪秀,范隆,徐国勋,等.丙泊酚和异氟醚麻醉对胰岛素抵抗及促炎细胞因子的影响[J].临床麻醉学杂志,2008,1,12(1):8-10
[3] Fernandez-Veledo S,HernandezR,TeruelT,etal.Ceramidemediates TNF-alpha-induced insulin resistance on GLUT4 gene expression in brown adipocytes[J]. Arch PhysiolBiochem, 2006, 112(1): 13-22.
[4] JoveM,PlanavilaA,Sanchez R M,etal. Palmitate induces tumor necrosis factor-alpha expression in C2C12skeletalmuscle cells by a mechanism involving protein kinase C and nuclear factor-kappaB activation[J]. Endocrinology, 2006, 147(1): 552-561.
[5] Kim HE,Tumour necrosis factor-alpha-induced glucose-stimulated insulin secretion inhibition in INS-1 cells is ascribed to a reduction of the glucose-stimulated Ca2+ influx. J Endocrinol. 2008 Sep;198(3):549-60. Epub 2008 Jul 1.
[6] Aljada A,Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells Metabolism. 2002 Apr;51(4):487-91.
[7] Gravlee GP,Davis RF,Utley JR,etal.Cardiopulmonary bypass:principles and practice. Baltimore:williams &wilkins, 1993. 513-519.
[8]隋东虎,石应康,王儒蓉,等.体外循环缺血一再灌注后心肌胰岛素抵抗现象的初步研究.中国胸心血管外科临床杂志,2001,8(1)28-31.10.
[9]隋东虎,石应康,王儒蓉,等.体外循环缺血一再灌注后心肌胰岛素抵抗与心功能障碍的关系.中华实验外科杂志,2002,19(3):208-210.
[10] PietersenHGLnagenbergCJGeskesG,etal.Myoeardial substrate uptake and oxidation during and after routin cardiac surgery . JThorae cardlovaseSurg,1999,118(l):71一80.
[11]王天龙,于德水,张京范.心脏外科围术期应用尼卡地平对心肌能量代谢的影响.中华麻醉学杂志,2001,1(2):73一76.
[12] Cendan JC,MD,SoubaWW,MD,ScD,etal. Cytokines regulate endotoxin stimulation of endothelial cell arginine transport.Surgery1995;117:213一9.
[13] Engelman DT,MD,Watanable M,MD Manlik N,PhD,etal.L-Arginine reduces endothelial inflammation and myocardialStunning during ischemial reperfusion.Ann Thoracsurg1995;60:1275一81.
[14] Angele MK,MD,Smail N,MD,Ayala A,PhD,etal.L-Arginine: a unique amino acid for restoring the depressed macrophage functions after trauma-hemorrhage.Jtrauma1999:46(1):34-9.
[15] Hiramatsu T,MD,Forbess JM,MD,Miura T,MD,etal.Effects of L-arginine and L-nitro-arginine methyl ester on recovery of neonatal lamb hearts after cold ischemia.JThoracCardiovace Surg1995;109:81-1.
[16]熊卫明,邱建,李志梁,等L-精氨酸对体外循环后血浆细胞因子及肌钙蛋白的影响[J]使用医学杂志,2003,15(5)474-475.
[17]林丽娜,王万铁,徐正衸等.左旋精氨酸对体外循环缺血再灌注损伤心肌的保护作用[J]中国胸心血管外科临床杂志,2000,5(2):89
[18]杜智勇,史忠,杨天德,等.体外循环心内直视术中胰岛素受体TPK活性的变化及意义[J].体外循环杂志,2002,4:81-87.
[19] Kuntschen FR,Galletti PM,Hahn C,etal. Alterations of insulin and glucose metabolism during cardiopulmonary bypass under normothermia[J]. J. Thorac Cardiovascu Surg. 1985,89:97-106.
[20]Kuntschen F R,Galletti PM,Hahn C,etal.Glucose-insulin interactions during cardiopulmonary bypass. Hypothermia versus normothermia[J]. J. Thorac Cardiovascu Surg. 1986,91:451-459.
[21] Lehot J J, PirizH,Villard J,etal. Glucose homeostasis. Comparison between hypothermic and normothermic cardiopulmonary bypass[J]. Chest. 1992 Jul; 102(1): 106-11 .
[22]体外循环研究与实践(龙村主编)[M].北京医科大学出版社,2000,58.
[23]徐建军,陈琳,胡大仁,等.体外循环手术病人胰腺内、外分泌功能的变化[J].江西医学院学报2000.12.31; 40(4): 25-27.
[24] McKnight C K,ElliottM J,Pearson DT,et al. The effects of four different crystalloid bypass pump-priming fluids upon the metabol response to cardiac operation[J]. J-Thorac-Cardiovasc-Surg1985 Jul; 90(1): 97-111.
[25] Sebel PS,Bovill J G, SchellekensAP,et al. Hormonal responses to high-dose fentanyl anaesthesia. Astudy in patients undergoing cardiac surgery[J]. Br-J-Anaesth. 1981 Sep; 53(9): 941-948.
[26]黑飞龙,龚菁,胡强等.围体外循环期肿瘤坏死因子与胰岛素抵抗[J].中国体外循环杂志, 2003, 1: 72-74.
[27] Mescheryakov AV,Kozlov I A, Dementyeva I I,et al. Glucose metabolism and insulin activity during cardiac surgery[J]. J-Cardiothorac-Anesth. 1989 Oct; 3(5): 536-543.
[28] McPheed,S J.etal. Pathophisiology of Disease[J]. (3rd version). McGraw-Hill,2000, 434-436.
[29]杜智勇.应激与胰岛素抵抗[M].国外医学·麻醉学与复苏分册2001.02.15; 22(1): 10-13.
[30] Takayama S,Kahn C R,Kubo K,et al. Alterations in insulin receptor autophosphorylation in insulin resistance: correlation with altered sensitivity to glucose transport and antilipolysis to insulin[J]. J Clini Endocrin Metab,1988, Vol 66, 992-999.
[31] GerasimosP,Sykiotis,AthanasiosG.etal. Serine Phosphorylation of Insulin Receptor Substrate-1: ANovel Target for the Reversal of Insulin Resistance [J].Molecular Endocrinology, 2001, 15(11): 1864-1869.
[32] Beauloye C,Bertrand L,Krause U,etal. No-FlowIschemia Inhibits Insulin Signaling in Heart by Decreasing Intracellular pH[J]. Circulation Research. 2001;88:513.
[33] Tappy L, Randin D,Vollenweider P,et al. Mechanisms of dexamethasone-induced insulinresistance in healthy humans[J]. J.Clin. Endocrinol. Metab., 1994,79:1063-1069.
[34] Qi C,Pekala PH. Tumor necrosis factor-alpha-induced insulin resistance in adipocytes[J]. Proc-Soc-Exp-Biol-Med. 2000Feb; 223(2): 128-35 .
[35] Raticliffe JM,thorac cardiovasc surgenon ,1988;36:65.
[36] Uchtenberg RC ,J lab Clin Med ,1993;121-697.
[37] wasserman K , circulation ,1989;80;1084.
[38] Roytblat, L,Rachinsky, M, Fisher, A,et al Raised Interleukin-6 Levels in Obese Patients. Obes Res. 2000;8:673–675.
[39] Straczkowski, M,Dzienis-Straczkowska, S, Stepien, A,et al, Plasma Interleukin-8 Concentrations Are Increased in Obese Subjects and Related to Fat Mass and Tumor Necrosis Factor-{alpha} System. J Clin Endocrinol Metab. 2002;87:4602–4606.
[40] Hotamisligil, GS, Spiegelman, BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes. 1994;43:1271–1278.
[41] Sartipy, P, Loskutoff, DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. PNAS. 2003;100:7265–7270.
[42] Hotamisligil, GS, Arner, P, Caro, JF,et al Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[43] Visser, M, Bouter, LM,McQuillan, GM,et al ,Elevated C-Reactive Protein Levels in Overweight and Obese Adults. JAMA. 1999;282:2131–2135.
[44] Van Snick J.Interleukin-6: an overview. Annu Rev Immunol 1990;8:253-78.
[45]Fong Y,Moldawer LL,Marano M,etal.Endotoxemia elicits increased circulating B2-IFN/IL-6 in man. J Immunol1989;142: 2321-4.
[46] Zhang Y,Lin J-X,Yip YK,Vilcek J.Stimulation of Interleukin-6 mRNA levels by tumor necrosis factor and interleukin-1.Ann N Y Acad Sci 1989;557:548-9.
[47] Pullicino EA,Carli F,Poole S,etal.The relationship between the circulatingconcentrations of interleukin-6(IL6),tumor necrosis factor(TNF)and the acute phase response to elective surgery and accidental injury.Lymph Res 1990;9:231-8.
[48] Coceani F,Lees J,Mantilla J,etal.Interleukind and tumor necrosis factor in cerebrospinal fluid: changes during pyrogen fever.Brain Res 1993:612:165-71.
[49] Hennein HA,Ebba H,Rodriguez JL,etal.Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularisation.J Thorac Cardiovasc Surg 1994;108:626-35.
[50] Finkel MS,Oddis CV,Jacob TD,etal.Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992;257:387-9.
[51] Finkel MS.Hoffman RA.Shen L.etal.Interleukin-6(IL-6) as a mediator of stunned myocardium. Am J Cardiol 1993;71: 1231-2.
[52] Matsushima K,Taguchi M,Kovacs EJ,etal.Intracellular localization of human monocyte associated interleukin-1(IL-1)activity and release of biologically active IL-1 from monocytes by trypsin and plasmin.J Immunol 1986;136:2883-91.
[53]Tabardel Y,Duchateau J,Schmartz D,etal.Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men. Surgery 1996;119:76-80.
[54]Martinez-Pellus AE,Merino I’,Bru M,etal.Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by the cardiopulmonary bypass? Crit Care Med 1993;21:1684-91.
[55]Butler J,Baigrie RJ,Parker D,etal. Systemic inflammatory responses to cardiopulmonary bypass: a pilot study of the effects of pentoxifylline. Respir Med 1993;87:285-8.
[56] Markewitz A,Faist E,Lang S,etal.Regulation of acute phase response after cardiopulmonary bypass by immunomodulation. Ann Thorac Surg 1993;55:389-94.
[57] Markewitz A,Faist E,Lang S,etal.Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation. J Thorac Cardiovasc Surg 1993;105: 15-24.
[58] Markewitz A, Faist E,Weir&old C,etal. Alterations of cell mediated immune response following cardiac surgery. Eur J Cardiothorac Surg 1993;7:193-9.
[59] Menasche I’,Haydar S,Peynet J,etal. A potential mechanism of vasodilation after warm heart surgery: the temperature dependent release of cytokines. J Thorac Cardiovasc Surg 1994; 107293-9.
[60]Ohata T,Sawa Y,Kadoba K,etal.Normothermia has beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions. ASAIO J 1995;41:M288-91.
[61]Sawa Y,Shimazaki Y,Kadoba K,etal.Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations. J Thorac Cardiovasc Surg 1996;111:29-35.
[62]Hill GE,Snider S,Galbraith TA,etal.Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass.Am J Respir Crit Care Med 1995;152:1791-5.
[63] Kawamura T,Inada K,Okada H,etal. Methylprednisolone inhibits increase of interleukin8 and 6 during open heart surgery. Can J Anaesth 1995;42:399-403.
[64] Kawamura T,Inada K,Akasaka N,Wakusawa R.Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery.Can J Anaesth 1996;43:456-60.
[65] Millar AB,Armstrong L,van der Linden J,etal. Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass.Ann Thorac Surg 1993;56:1499-502.
[66] Joumois D,Pouard I’,Greeley WJ, etal. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery: effects on hemostasis,cytokines,and complement components. Anes- thesiology 1994;81:1181-9.
[67]Joumois D,Pouard I’,Rolland B, Lagarde M.Ultrafiltration allows to reduce cytokine plasma concentrations during pediatric cardiopulmonary bypass.Contrib Nephrol1995;116:86-8.
[68] Johnson D,Thomson D,Mycyk T,etal.Depletion of neutrophils by filter duringaortocoronary bypass surgery transiently improves postoperative cardiorespiratory status. Chest 1995; 1071253-9.
[69]Wang Ming J,Chiu IS,Hsu CM,etal.Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations.Ann Thorac Surg 1996;61:651-6.
[70]Butler J,Chong GL,Baigrie RJ,etal.Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 1992;53:833-8.
[71]Weerwind PW,Maessen JG,van Tits LJH,et al.Influence of Duraflo II heparin-treated extracorporeal circuits on the systemic inflammatory response in patients having coronary bypass. J Thorac Cardiovasc Surg 1995;110:1633-41.
[72] Gullestad L,Aukrust P,The cytokine network in heart failure ;pathgenetic importance and potential theurapeutic target[J] heart failure monit ,2001,2(1):8-13
[73] Senn JJ,KloverPJ, Nowak IA,et al. Interleukin induces cellular insulin resistance in hepatocytes.Diabetes, 2002, 51: 3391-9.
[74] Kopp, HP, et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003;23:1042–7.
[75] Fontana, L, Eagon, JC, Trujillo, ME, etal,Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010–3.
[76] Klover, PJ, Clementi, AH,Mooney, RA. Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology. 2005;146:3417–27.
[77]Wallenius V,Interleukin-6-deficient mice develop mature-onset obesity.Nat Med. 2002;8:75–9.
[78] Di Gregorio, GB, Hensley, L, Lu, T,et al. Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am J Physiol Endocrinol Metab. 2004;287:E182–7.
[79] Flier, JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell. 2004;116:337–50.
[80] Wernstedt I, Edgley A,Berndtsson A,etal, Reduced stress and coldinduced increase in energy expenditure in interleukin-6-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2006;291:R551–7.
[81] Yoshimura T,Matsushima K,Oppenheim JJ,etal.Neutrophil chemotactic factor produced by lipopolysaccharide(LPS)stimulated human blood mononuclear leukocytes:partial characterization and separation from interleukin1(IL -1). J Immunol 1987;139:788-93.
[82] Thelen M,Peveri P,Kernen I’,etal.Mechanism of neutrophil activation by NAF,a novel monocyte derived peptide agonist. FASEB J 1988;2:2702-6.
[83] Huber A,Kunkel SL,Todd RF III,etal.Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science 1991;254:99-102.
[84] Colditz IG,Zwahlen RD,Baggiolini M.Neutrophil accumulation and plasma leakage induced in vivo by neutrophil activating peptide1. J Leuk Biol 1990;48:129-37.
[85] Inaba H,Kochi A,Yorozu S.Suppression by methylprednisolone of augmented plasma endotoxin like activity and interleukin-6 during cardiopulmonary bypass.Br J Anaesth 1994; 72:348-50.
[86] Engelman RM,Rousou JA,Flack JE III,etal.Influence of steroids on complement and cytokine generation after cardiopulmonary bypass.AM Thorac Surg 1995;60:801-4.
[87] Finn A,Naik S,Klein N,etal.Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;105:234-41.
[88] Kawamura T,Wakusawa R,Okada K,Inada S.Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin8 and 6 in reperfusion injury. Can J Anaesth 1993;40:1016-21.
[89] Finn A,Moat N,Rebuck N,etal.Changes in neutrophil CDllb/CD18 and I-selectin expression and release of interleukin 8 and elastase in paediatric cardiopulmonary bypass.Agents Actions 1993;38:C44-6.
[90] Jorens PG,de Jongh R,de Backer W,etal.Interleukin-8 production in patients undergoing cardiopulmonary bypass:the influence of pretreatment with methylprednisolone. Am Rev Respir Dis 1993;148:890-5.
[91]Sheron N,Williams R.IL-8 as a circulating cytokine:induction by recombinant tumour necrosis factor-alpha. Clin Exp Immuno1 1992;89:100-3.
[92]Tiinz M,Mihaljevic T,von Segesser LK,etal.Acute lung injury during cardiopulmonary bypass: are the neutrophils responsible? Chest 1995;108:1551-6.
[93] Burns SA,Newburger JW,Xiao M,et al.Induction of interleukin-8 messenger RNA in heart and skeletal muscle during pediatric cardiopulmonary bypass.Circulation 1995; 92(Suppl 11):315-21.
[94] El Habbal MH,Carter H,Smith LJ,etal.Neutrophil activation in paediatric extracorporeal circuits:effect of circulation and temperature variation.Cardiovasc Res 1995;29:102-7.
[95]McBride WT,Armstrong MA,Crockard AD,etal.Cytokine balance and immunosuppressive changes at cardiac surgery: contrasting response between patients and isolated CPB circuits. Br J Anaesth 1995;75:724-33.
[96]de Waal Malefyt R,Abrams J,Bennett B,et al.Interleukin-10(IL-l0) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991;174:1209-20.
[97]Chernoff AE, Granowitz EV,Shapiro L,etal.A randomized,controlled trial of IL-10 in humans. J Immunol1995;154:5492-9.
[98] Seghaye Marie-C,Duchateau J,Bruniaux J,etal.Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg 1996;lll:
[99] Stefano GB,Rodriguez M,Glass R, etal.Hyperstimulation of leukocytes by plasma fromcardiopulmonary bypass patients is diminished by morphine and IL-10 pretreatment.J Cardio- vast Surg 1995;36:25-30.
[100] Shottelius A., Mayo M.W., Sartor R.B.,etal. Interleukin-10 signaling blocks inhibitor of kB kinase activity and nuclear factor kB DNA binding. J Biol Chem 1999;274:31868-31874.
[101] van Exel E, Gussekloo J, de Craen AJ,et al .Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study. Diabetes. 2002;51:1088–92.
[102] Kim HJ, Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes. 2004;53:1060–7.
[103] Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175–84.
[104] Hotamisligil GS,Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
[105] Hotamisligil GS, Arner P, Caro JF,etal. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[106] Hotamisligil GS,Peraldi P, Budavari A,etal. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.
[107] Uysal KT, Wiesbrock SM, Marino MW,etal. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610–4.
[108] Stephens JM, Lee J,Pilch PF. Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem. 1997;272:971–6.
[109] Ruan H, Hacohen N,Golub TR,etal.Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes. 2002;51:1319–36.
[110] Leinonen E, Hurt-Camejo E,W iklund O,et al. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesionmolecules in type2 diabetes. Atherosclerosis, 2003, 166:387-94.
[111]The Systemic Inflammatory Response to Cardiopulmonary Bypass: Pathophysiological,Therapeutic,and Pharmacological Considerations[J]Anesth Analg 1997;85:766-782
[112]张拥军,肖诗亮,聂荣华,等.肿瘤坏死因子-α与体外循环中胰岛素抵抗的研究[J]临床外科杂志,2007,4,15(4):261-263.
[113] KirklinJK.ProsPect for understanding and eliminating the deleterious effects of cardiopulmonary bypass .[J]Ann thorac surg 1991;51:529-531
[114]Engellman DT,MD,Wantanable M,MD,Manlik,N,PhD,etal.L-Arginine reduces endothelial inflammation and myocardial stunning ischemia reperfusion.[J] AnnThoracsurg1995:60:1275-1281.
[115] Angele MK,MD,Smai1 N,MD,Ayala A,PhD,et al.L-Arginine:a unique amino acid for restoring the depressed macrophage funetions after trauma-hemorrhage.[J] Trauma. 1999 Jan;46(1):34-41.
[116]Clermont G,Vergely C,Cellular injury associated with extracorporeal circulation.[J]AnnCardiolAngeiol2002:51:38一43.
[117] Barbul, B. Arginine: biochemistry, physiology, and therapeutic implications.[J] Parenter Enteral Nutr. 1986;10:227–238.
[118] Wu, G,Morris,SM., Jr Arginine metabolism: nitric oxide and beyond. [J]Biochem J. 1998;336:1–17.
[119] Palmer RMJ,Ashton AS,Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine.[J] Nature. 1998;333:664–666.
[120] Loscalzo J, Welch G. Nitric oxide and its role in the cardiovascular system. [J]Prog Cardiovasc Dis. 1995;35:87–104.
[121] Durante W. Regulation of L-arginine transport and metabolism in vascular smooth muscle cells.[J] Cell Biochem Biophys. 2001;35:19–34.
[122] John S, Schmeider RE. Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia.[J] Curr Hypertens Rep. 2003;5:199–207.
[123] Soriano FG, Virag L, Szabo C. Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation. [J] Mol Med. 2001;79:437–448.
[124] Lefer Am, Lefer DJ.The role of nitric oxide and cell adhesion molecules on the microcirculation in ischemia-reperfusion.[J] Cardiovas Res. 1996;32:743–751.
[125] Drexler H, Zeiher AM, Meinzer K,etal.Correction of endothelial dysfunction in coronary microcirculation of hypercholestrolemic patients by L-arginine.[J] Lancet. 1991;67:1301–1308.
[126] Cooke JP, Singer AH, Tsao P,etal, Antiatherogenic effects of L-arginine in the hypercholestrolemic rabbit. [J ]Clin Invest. 1992;90:1168–1172.
[127] Tarry WC, Markhoul RG. L-Arginine improves endothelial-dependent vasorelaxation and reduces intimal hyperplasia after balloon injury.[J]ArteriosclerThromb. 1994;14:938–943.
[128] Loscalzo J.An experiment in nature: genetic L-arginine deficiency and NO insufficiency.[J] Clin Invest. 2001;108:663–664.
[129]刘庆.L-精氨酸对胰岛素抵抗大鼠血压及胰岛素抵抗[D]天津医科大学.2004
[130] Moncada S, Palmer RMJ, Higgs EA. Nitric oxide:physiology,pathophysiology, and pharmacology.[J] Pharmacol Rev, 1991, 43
[131] Furchgott RF,Carvaho MH.Evidence for endothelium-dependent vasodilation ofresistance vessels by acetylcholing.[J]Blood Vessels,1987,24(3):145-149.;1991, 43(2):109-142.;
[132] Furlong B, Henderson AM, Lewis MJ,etal. Endothelium-derived relaxing factor inhibits in vitro platelet. [J]Br J Pharmacol,1987, 90(4):687-692.
[133] Kubes P, Suzuki M, Granger DN. Nitric oxide:an endogenousmodulator of leukocyte adhesion. [J]Proc Natl Acad Sci USA,1991, 88(11):4651-4655,
[134] Rakoff JS, Sile JM, Sinha YN,et al. Prolactin and grouthhormone release in respomse to sequential stimulation by arginineand TRF.[J]Clin Eedocrinol Metab, 1973, 37(4):641-644.。
[135] Angele MK,MD,Smai1 N,MD,Ayala A,PhD,etal.L-Arginine:a unique amino acid for restoring the depressed macrophage functions after trauma hemorrhage.[J] Trauma1999:46(1):34-39.
[136] CendanJC,MD,Souba WW,MD,ScD,Edward M,etal.Cytokines regulate endotoxin stimulation of endothelial cell arginine transPort.[J]Surg1995;117:213-219.
[1] Thoerll A,Nygrne J,Essen P,et al. The metabolic response to cholecystectomy: insulin Resistance after open compared with laparoscopic operation.Eur J Surg.1996Mar;162(3):187一91.
[2]《体外循环学》,龙村主编,人民军医出版社,2004,1-17.
[3]SwanJW,WaltonC,GdeslandIF,Insulin resistance in chronic heart failure[J].EurHeartJ.1994,15(11):1528-32.
[4] Swna JW,Anker SD,Walton C,et al. Insulin resistance in chronic heart failure: Relation to severity and etiology of heart failure[J].JAmcollCardiol,1997,30(2):527-32.
[5] Clement K,Genetic variation in the beta 3-adrenergic receptor and Increased capacity to gain weight in Patients with morbid obesity[J].Nengl J Med,1995,333(6):352-4.
[6]李光伟,潘效仁,LinoijaS等.检测人群胰岛素抵抗的一项新指数[J].中华内科杂,1993,32(11):656-660.
[7]罗宗,秦文勇,胰岛素抵抗与充血性心力衰竭关系的研究[J]西藏科技.2009:2:51-52
[8] Giroir BP. Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade. Crit Care Med 1993;21:780-9.
[9] Blick M,Sherwin SA,Rosenblum M,et al .Phase I study of recombinant tumor necrosis factor in cancer patients. Cancer Res 1987;47:2986-9.
[10] Smith JW II,Urba WJ,Curti B,et al.The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies. J Clin Oncol 1992;l0: 1141-52.
[11] Kaushansky K,Broudy VC,Harlan JM,et al.Tumor necrosis factor and tumor necrosis factor-p (Lymphotoxin) stimulate the production of granulocyte-macrophage colony stimulating factor,macrophage colony stimulating factor,and IL-1 in vivo. J Immunol 1988;141:3410-5.
[12] Zhang Y, Lin J-X,Yip YK,et al. Stimulation of Interleukin-6 mRNA levels by tumor necrosis factor and interleukin-1. Ann N Y Acad Sci 1989;557:548-9.
[13] Matsushima K,Taguchi M,Kovacs EJ,et al.Intracellular localization of human monocyte associated interleukin 1 (IL-1) activity and release of biologically active IL-1 from monocytes by trypsin and plasmin. J Immunol 1986;136:2883-91.
[14] Inaba H,Kochi A,Yorozu S.Suppression by methylprednisolone of augmented plasma endotoxin like activity and interleukin-6 during cardiopulmonary bypass.Br J Anaesth 1994; 72:348-50.
[15] Engelman RM, Rousou JA,Flack JE III,et al. Influence of steroids on complement and cytokine generation after cardiopulmonary bypass. AM Thorac Surg 1995;60:801-4.
[16] Tabardel Y,Duchateau J,Schmartz D,et al.Corticosteroids increase blood interleukin-10 levels during cardiopulmonary bypass in men. Surgery 1996;119:76-80.
[17] Martinez-Pellus AE,Merino I’,Bru M,et al.Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by the cardiopulmonary bypass? Crit Care Med 1993;21:1684-91.
[18] Butler J,Baigrie RJ,Parker D,etal.Systemic inflammatory responses to cardiopulmonary bypass:a pilot study of the effects of pentoxifylline. Respir Med 1993;87:285-8.
[19] Markewitz A,Faist E, Lang S, et al.Regulation of acute phase response after cardiopulmonary bypass by immunomodulation. Ann Thorac Surg 1993;55:389-94.
[20] Markewitz A,Faist E,Lang S,etal.Successful restoration of cell-mediated immune response after cardiopulmonary bypass by immunomodulation.J Thorac Cardiovasc Surg 1993;105: 15-24.
[21] Markewitz A,Faist E, Weir&old C,et al.Alterations of cell mediated immune response following cardiac surgery. Eur J Cardiothorac Surg 1993;7:193-9.
[22] Menasche I’,Haydar S,Peynet J,et al.A potential mechanism of vasodilation after warmheart surgery:the temperature dependent release of cytokines.J Thorac Cardiovasc Surg 1994; 107293-9.
[23] Ohata T,Sawa Y,Kadoba K,et al.Normothermia has beneficial effects in cardiopulmonary bypass attenuating inflammatory reactions. ASAIO J 1995;41:M288-91.
[24] Murray DRFreeman GL.Tumor necrosis factor-alpha induces a biphasic effect on myocardial contractility in conscious dogs[J].Cier Res,1996,78(l):154一160.
[25] Lee RE,Lotze MT,Skibber JM,et al.Cardiorespiratory effects of immunotherapy with interleukin-2. J Clin Oncol 1989;7:7-20.
[26] Fujiwara T,Grimm EA.Specific inhibition of interleukin 1B gene expression by an antisense oligonucleotide:obligatory role of interleukin-1 in the generation of lymphokine activated killer cells. Cancer Res 1992;52:4954-9.
[27] Giovarelli M,Santoni A,Jemma C,et al.Obligatory role of IFN-y in induction of lymphokine-activated and T lymphocyte killer activity,but not in boosting of natural cytotoxicity.J Immunol 1988;141:2831-6.
[28] Van Snick J.Interleukin-6:an overview. Annu Rev Immunol 1990;8:253-78.
[29] Fong Y,Moldawer LL,Marano M,et al.Endotoxemia elicits increased circulating B2-IFN/IL-6 in man.J Immunol 1989;142: 2321-4.
[30] Hennein HA,Ebba H,Rodriguez JL,et al.Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularisation. J Thorac Cardiovasc Surg 1994;108:626-35.
[31] Finkel MS,Oddis CV,Jacob TD,et al.Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 1992;257:387-9.
[32] Coceani F,Lees J,Mantilla J,et al.Interleukind and tumor necrosis factor in cerebrospinal fluid: changes during pyrogen fever. Brain Res 1993:612:165-71.
[33] Pullicino EA,Carli F,Poole S,et al.The relationship between the circulating concentrations of interleukin-6(IL6),tumor necrosis factor(TNF) and the acute phaseresponse to elective surgery and accidental injury.Lymph Res 1990;9:231-8.
[34] Finkel MS.Hoffman RA.Shen L.et al.Interleukin-6(IL-6) as a mediator of stunned myocardium. Am J Cardiol 1993;71: 1231-2.
[35] Sawa Y,Shimazaki Y,Kadoba K,etal.Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations.J Thorac Cardiovasc Surg 1996;111:29-35.
[36] Hill GE,Snider S,Galbraith TA,etal.Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass.Am J Respir Crit Care Med 1995;152:1791-5.
[37] Kawamura T,Inada K,Okada H,et al.Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery. Can J Anaesth 1995;42:399-403.
[38] Kawamura T,Inada K,Akasaka N,Wakusawa R.Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery.Can JAnaesth 1996;43:456-60.
[39] Millar AB,Armstrong L,van der Linden J,etal.Cytokine production and hemofiltration in children undergoing cardiopulmonary bypass. Ann Thorac Surg 1993;56:1499-502.
[40] Joumois D,Pouard I’,Greeley WJ,etal. Hemofiltration during cardiopulmonary bypass in pediatric cardiac surgery:effects on hemostasis,cytokines, and complement components. Anesthesiology 1994;81:1181-9.
[41] Joumois D,Pouard I’, Rolland B,Lagarde M.Ultrafiltration allows to reduce cytokine plasma concentrations during pediatric cardiopulmonary bypass.Contrib Nephrol1995;116:86-8.
[42] Johnson D,Thomson D,Mycyk T,etal.Depletion of neutrophils by filter during aortocoronary bypass surgery transiently improves postoperative cardiorespiratory status. Chest 1995; 1071253-9.
[43] Wang Ming J,Chiu IS,Hsu CM,etal.Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations.Ann Thorac Surg 1996;61:651-6.
[44] Butler J,Chong GL,Baigrie RJ,etal.Cytokine responses to cardiopulmonary bypass with membrane and bubble oxygenation. Ann Thorac Surg 1992;53:833-8.
[45] Weerwind PW,Maessen JG,van Tits LJH,etal.Influence of Duraflo II heparin-treated extracorporeal circuits on the systemic inflammatory response in patients having coronary bypass. J Thorac Cardiovasc Surg 1995;110:1633-41.
[46] Yoshimura T,Matsushima K,Oppenheim JJ,Leonard EJ.Neutrophil chemotactic factor produced by lipopolysaccharide(LPS) stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin-1(IL-1).JImmunol 1987;139:788-93.
[47] Thelen M,Peveri P,Kernen I’,etal.Mechanism of neutrophil activation by NAF,a novel monocyte derived peptide agonist.FASEB J 1988;2:2702-6.
[48] Huber A,Kunkel SL,Todd RF III,etal.Regulation of transendothelial neutrophil migration by endogenous interleukin-8.Science 1991;254:99-102.
[49] Colditz IG,Zwahlen RD,Baggiolini M.Neutrophil accumulation and plasma leakage induced in vivo by neutrophil activating peptide-1.J Leuk Biol 1990;48:129-37.
[50] Jorens PG,de Jongh R,de Backer W,et al.Interleukin-8 production in patients undergoing cardiopulmonary bypass:the influence of pretreatment with methylprednisolone.Am Rev Respir Dis 1993;148:890-5.
[51] Finn A,Naik S,Klein N,etal.Interleukin-8 release and neutrophil degranulation after pediatric cardiopulmonary bypass. J Thorac Cardiovasc Surg 1993;105:234-41.
[52] Kawamura T,Wakusawa R,Okada K,Inada S.Elevation of cytokines during open heart surgery with cardiopulmonary bypass:participation of interleukin-8 and 6 in reperfusion injury. Can J Anaesth 1993;40:1016-21.
[53] Finn A,Moat N,Rebuck N,etal.Changes in neutrophil CDllb/CD18 and I-selectin expression and release of interleukin-8 and elastase in paediatric cardiopulmonary bypass. Agents Actions 993;38:C44-6.
[54] Sheron N,Williams R.IL-8 as a circulating cytokine:induction by recombinant tumournecrosis factor-alpha. Clin Exp Immuno1 1992;89:100-3.
[55] Tiinz M,Mihaljevic T von Segesser LK,etal.Acute lung injury during cardiopulmonary bypass:are the neutrophils responsible? Chest 1995;108:1551-6.
[56] Burns SA,Newburger JW,Xiao M,etal.Induction of interleukin-8 messenger RNA in heart and skeletal muscle during pediatric cardiopulmonary bypass.Circulation 1995; 92(Suppl 11):315-21.
[57] El Habbal MH,Carter H, Smith LJ,etal.Neutrophil activation in paediatric extracorporeal circuits:effect of circulation and temperature variation.Cardiovasc Res 1995;29:102-7.
[58] Kharazmi A,Andersen LW,Baek L,etal.Endotoxemia and enhanced generation of oxygen radicals by neutrophils from patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989;98:381-5.
[59] cavarocchi NC,England MD,Schaff HV,etal.Oxygen free radical generation during cardiopulmonary bypass:correlation with complement activation. Circulation 1986;74(Suppl III): 130-3.
[60] Sinclair DG, Haslam PL,Quinlan GJ,etal.The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability.Chest 1995;108:718-24.
[61] Davies SW,Underwood SM,Wickens DG,etal.Systemic pattern of free radical generation during coronary bypass surgery.Br Heart J 1990;64:236-40.
[62] Schorer AE,Moldow CF,Rick ME.Interleukin-1 or endotoxin increases the release of von Willebrand factor from human endothelial cells.Br J Haematol 1987;67:193-7.
[63] Elliott MJ,Finn AHR.Interaction between neutrophils and endothelium.Ann Thorac Surg 1993;56:1503-8.
[64] Fosse E,Mollnes TE,Osterud A,etal.Effects of methylprednisolone on complement activation and leukocyte counts during cardiopulmonary bypass.Stand J Thorac Cardiovasc Surg 1987;21:255-61.
[65] Jansen NJG,van Oeveren W, Broek Lvd, et al.Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass.J Thorac Cardiovasc Surg 1991;102:515-25.
[66] van Oeveren W,Jansen NJG,Bidstrup BP,etal.Effects of aprotinin on hemostatic mechanisms during cardiopulmonary bypass.Ann Thorac Surg 1987;44:640-5.
[67]Taggart DP,Sundaram S,McCartney C,etal.Endotoxemia,complement,and white blood cell activation in cardiacsurgery:a randomized trial of laxatives and pulsatile perfusion.Ann Thorac Surg 1994;57:376-82.
[68] Jansen PGM,Te Velthuis H,Wildevuur WR,etal.Cardiopulmonary bypass with modified gelatin and heparin coated circuits.Br J Anaesth 1996;76:13-9.
[69] Dapper F,Neppl H,Wozniak G,etal.Influence of 4 different membrane oxygenators on inflammation like processes during extracorporeal circulation with pulsatile and non-pulsatile flow.Eur J Cardiothorac Surg 1992;6:18-24.
[70] Driessen JJ,Dhaese H,Fransen G,etal.Pulsatile compared with nonpulsatile perfusion using a centrifugal pump for cardiopulmonary bypass during coronary bypass grafting: effects on systemic haemodynamics,oxygenation,and inflammatory response parameters. Perfusion 1995;10:3-12.
[71]Nilsson L,Nilsson U,Venge I’,etal.Inflammatory system activation during cardiopulmonary bypass as an indicator of biocompatibility: a randomized comparison of bubble and membrane oxygenators. Stand J Thorac Cardiovasc Surg 1990; 24:53-8.
[72] Nilsson L,Tyden H,Johansson o,etal.Bubble and membrane oxygenators:comparison of postoperative organ dysfunction with special reference to inflammatory activity.Stand J Thorac Cardiovasc Surg 1990;24:59-64.
[73] Gillinov AM,Bator JM,Zehr KJ,etal.Neutrophil adhesion molecule expression during cardiopulmonary bypass with bubble and membrane oxygenators.Ann Thorac Surg 1993;56: 847-53.
[74]Gu YJ,van Oeveren W,Akkerman C,etal.Heparin coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:917-22.
[75] Fosse E,Moen 0,Johnson E,etal.Reduced complement and granulocyte activation with heparin coated cardiopulmonary bypass.Ann Thorac Surg 1994;58:472-7.
[76] Hatori N,Yoshizu H,Haga Y,etal.Biocompatibility of heparin coated membrane oxygenator during cardiopulmonary bypass.Artif Organs 1991;18:904-10.
[77] Pekna M,Borowiec J,Fagerhol MK,etal.Biocompatibility of heparin coated circuits used in cardiopulmonary bypass. Stand J Thorac Cardiovasc Surg 1994;28:5-11.
[78]McBride WT,Armstrong MA,Crockard AD,etal.Cytokine balance and immunosuppressive changes at cardiac surgery:contrasting response between patients and isolated CPB circuits.Br J Anaesth 1995;75:724-33.
[79] De Waal Malefyt R,Abrams J,Bennett B,etal.Interleukin-10 (IL-l0)inhibits cytokine synthesis by human monocytes:an autoregulatory role of IL-10 produced by monocytes.J Exp Med 1991;174:1209-20.
[80] Chernoff AE,Granowitz EV,Shapiro L,etal.A randomized, controlled trial of IL-10 in humans.J Immunol1995;154:5492-9.
[81] Seghaye Marie C,Duchateau J,Bruniaux J,etal.Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations. J Thorac Cardiovasc Surg 1996;lll:
[82] Stefano GB, Rodriguez M,Glass R,etal.Hyperstimulation of leukocytes by plasma from cardiopulmonary bypass patients is diminished by morphine and IL-10 pretreatment.J Cardio- vast Surg 1995;36:25-30.
[83] Shottelius A,Mayo M.W.,Sartor R.B.,et al. Jr Interleukin-10 signaling blocks inhibitor of kB kinase activity and nuclear factor kB DNA binding. J Biol Chem 1999;274:31868-31874.
[84] D.Paparellaa*,T.M. Yaua, E. Youngb ,et al .Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update Eur J Cardiothorac Surg 2002;21:232-244.
[85] Chenoweth D.E.,Cooper S.W.,Hugli T.E.,etal.BlackstoneE.H., Kirklin J.W.Complement activation during cardiopulmonary bypass:evidence for generation of C3a and C5a anaphylotoxins. N Engl J Med 1981;304:497-503.
[86] Bruins P.,te Velthuis H.,Yazdanbakhsh A.P.,etal.Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation 1997;96:3542-3548.
[87] Gu J.Y.,Mariani M.A.,Boonstra P.W.,etal.Complement activation in coronary artery bypass grafting patients without cardiopulmonary bypass. Chest 1999;116:892-898.
[88] Kyriakides C.,Wang Y.,Austen W.G,etal.Moderation of skeletal muscle reperfusion injury by a sLex-glycosylated complement inhibitory protein.Am J Physiol Cell Physiol 2001;281:C224-C230.
[89] Giroir B.P. Mediators of septic shock: new approaches for interrupting the endogenous inflammatory cascade. Crit Care Med 1993;21:780-789.
[90] Jirik F.R., Podor T.J., Hirano T.,etal.Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol 1989;142:144-147.
[91] Andersen L.W.,Landow L.,Baek L.,etal. Association between gastric intramucosal ph and splanchnic endotoxin, antibody to endotoxin, and tumor necrosis factor- concentration in patients undergoing cardiopulmonary bypass. Crit Care Med 1993;21:210-217.
[92]Riddington D.W.,Venkatesh B.,Boivin C.M.,etal.Intestinal permeability,gastric intramucosal ph, and systemic endotoxemia in patients undergoing cardiopulmonary bypass. J Am Med Assoc 1996;275:1007-1012.
[93] Lequier L.L.,Nikaidoh H.,Leonard S.R.,et al.Preoperative and postoperative endotoxemia in children with congenital heart disease. Chest 2000;117:1706-1712.
[94] Busse R,Mulsch A.Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett 1990;275: 87-90.
[95] Petros A,Bennett D,Valiance I’.Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock.Lancet 1991;338:1557-8.
[96] Kubes I’,Suzuki M,Granger DN.Nitric oxide:an endogenous modulator of leukocyte adhesion.Proc Nat1 Acad Sci USA 1991;88:4651-5.
[97]Moncada I,Higgs A.The L-arginine-nitric oxide pathway.N Engl J Med 1993;329:2002-12.
[98] Matheis G,Sherman Ml’,Buckberg GD,etal.Role of L-arginine-nitric oxide pathway in myocardial reoxygenation iniury. Am 1 Phvsiol 1992:262:H616-20.
[99] Delgado R,*Rojas A,Glaria LA,etal.Ca’+-independent nitric oxide synthase activity in human lung after cardiopulmonary bypass.Thorax 1995;50:403-4.
[100] Moncada S.,Higgs A.Mechanisms of disease: the L-arginin-nitric oxide pathway. N Engl J Med 1993;329:2002-2012.
[101] Worrall N.K., Chang K., Lejeunne W.S.,etal.TNF- causes reversible in vivo systemic vascular barrier dysfunction via NO-dependent and -independent mechanisms. Am J Physiol 1997;273:H2565-H2574.
[102] Oyama J.,Shimokawa H.,Momii H.,et al.Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo.J Clin Invest 1998;101:2207-2214.
[103] Sato H.,Zhao Z.Q.,Todd J.C.,etal.Basal nitric oxide expresses endogenous cardioprotection during reperfusion by inhibition of neutrophil-mediated damage after surgical revascularization. J Thorac Cardiovasc Surg 1997;113:399-409.
[104] Engelman D.T.,Watanabe M.,Engelman R.M.,etal.Constitutive nitric oxide release is impaired after ischemia and reperfusion. J Thorac Cardiovasc Surg 1995;110:1047-1053.
[105] Christman J.W.,Lancaster L.H.,Blackwell T.S. Nuclear factor k B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med 1998;24:1131-1138.
[106] Baldwin A.S.,Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996;14:649-683.
[107] Li C.,Browder W.,Kao R.L.Early activation of transcription factor NF-kB during ischemia in perfused heart rat. Am J Physiol 1999:H543-H552.
[108] Oitzinger W.,Hofer-Warbinek R.,Schmid J.A.,etal. Adenovirus-mediated expression of a mutant IkB kinase 2 inhibits the response of endothelial cells to inflammatory stimuli. Blood 2001;97:1611-1617.
[109] Ilton M.K.,Langton P.E.,Taylor M.L.,etal.Differential expression of neutrophil adhesion molecules during coronary artery surgery with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1999;118:930-937.
[110] Jordan J.E.,Zhao Z.Q.,Vinten-Johansen J.The role of neutrophils in myocardial ischemia–reperfusion injury. Cardiovasc Res 1999;43:860-878.
[111] Zahler S.,Massoudy P.,Hartl H.,etal.Acute cardiac inflammatory response to postischemic reperfusion during cardiopulmonary bypass. Cardiovasc Res 1999;41:722-730.
[112] Wahba A.,Rothe G.,Lodes H.,etal.Effects of extracorporeal circulation and heparin on the phenotype of platelet surface antigens following heart surgery.Thromb Res 2000;97:379-386.
[113] Roytblat L,Rachinsky, M,Fisher A,etal.Raised Interleukin-6 Levels in Obese Patients. Obes Res. 2000;8:673–675.
[114] Straczkowski M,Dzienis-Straczkowska S,Stepien A,etal.Plasma Interleukin-8 Concentrations Are Increased in Obese Subjects and Related to Fat Mass and Tumor Necrosis Factor-{alpha} System. J Clin Endocrinol Metab. 2002;87:4602–4606.
[115] Hotamisligil GS, Spiegelman BM.Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes. 1994;43:1271–1278.
[116] Sartipy P,Loskutoff DJ.Monocyte chemoattractant protein 1 in obesity and insulin resistance. PNAS. 2003;100:7265–7270.
[117] Hotamisligil GS,Arner P,Caro JF,etal.Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[118]Visser M,Bouter LM,McQuillan GM,etal.Elevated C-Reactive Protein Levels in Overweight and Obese Adults. JAMA. 1999;282:2131–2135.
[119] Leinonen E,Hurt-Camejo E,W iklund O,etal. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesionmolecules in type 2 diabetes. Atherosclerosis, 2003, 166:387-94.
[120] Cone RD.Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8:571–8.
[121] de Luca C,Olefsky JM.Stressed out about obesity and insulin resistance. Nat Med. 2006;12:41–2. discussion 42.
[122] Yu C,Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem. 2002;277:50230–6.
[123] Pickersgill L,Litherland GJ, Greenberg AS,etal.Key role for ceramides in mediating insulin resistance in human muscle cells. J Biol Chem. 2007
[124] Lee JS, Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites. J Appl Physiol. 2006;100:1467–74.
[125] Taniguchi CM,Emanuelli B,Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol. 2006;7:85–96.
[126] Aguirre V,Werne ED Giraud J,etal.Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action. J Biol Chem. 2002;277:1531–1537.
[127]Rui L,Yuan M,Frantz D,etal.SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem. 2002;277:42394–8.
[128] Imamura T,G alpha-q/11 protein plays a key role in insulin-induced glucose transport in 3T3-L1 adipocytes. Mol Cell Biol. 1999;19:6765–74.
[129] Usui I,Imamura T, Huang J,etal. Cdc42 is a Rho GTPase family member that can mediate insulin signaling to glucose transport in 3T3-L1 adipocytes. J Biol Chem. 2003;278:13765–74.
[130] Baumann CA, CAP defines a second signalling pathway required for insulin-stimulated glucose transport. Nature. 2000;407:202–7.
[131] Hotamisligil GS,Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
[132]Hotamisligil GS,Arner P,Caro JF,etal.Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest. 1995;95:2409–15.
[133] Hotamisligil GS,Peraldi P,Budavari A,etal.IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.
[134] Uysal KT,Wiesbrock SM,Marino MW,etal.Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature. 1997;389:610–4.
[135] Stephens JM,Lee J,Pilch PF. Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. J Biol Chem. 1997;272:971–6.
[136] Ruan H,Hacohen N,Golub TR,etal.Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes. 2002;51:1319–36.
[137] Hotamisligil GS,Shargill NS,Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.
[138] Dandona P,Weinstock R,Thusu K,etal. Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab. 1998;83:2907–10.
[139] Paz K,Hemi R,LeRoith Detal.A molecular basis for insulin resistance: elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation. J Biol Chem. 1997;272:29911–8.
[140] Aguirre V,Uchida T,Yenush L,etal. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem. 2000;275:9047–54.
[141] Yang R, Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese mice. J Biol Chem. 2007;282:22765–74.
[142] Tuncman G,Hirosumi J,Solinas G,etal. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci U S A. 2006;103:10741–6.
[143]Yuan M,Konstantopoulos N,Lee J,et al. Reversal of obesityand diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science. 2001;293:1673–7.
[144]Yin MJ,Yamamoto Y,Gaynor RB.The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature. 1998;396:77–80.
[145] Ebstein W.Zur Therapie des Diabetes mellitus, insbesondereüber die Anwendung des salicylsauren Natron bei demselben. Berliner Klinische Wochenschrift. 1876;13:337–40.
[146] Cai D,Yuan M,Frantz DF,etal.Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11:183–90.
[147] Arkan MC,etal.IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med. 2005;11:191–8.
[148] Williamson RT,Lond MD.On the treatment of glycosuria and diabetes mellitus with sodium salicylate. British Med J. 1901;1:760–762.
[149] Kim JK,etal.Prevention of fat-induced insulin resistance by salicylate. J Clin Invest. 2001;108:437–46.
[150]Sugita H,Fujimoto M,Yasukawa T,etal.Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem. 2005;280:14203–11.
[151] Yasukawa T,Tokunaga E,Ota H,etal.S-nitrosylation-dependent inactivation of Akt/protein kinase B in insulin resistance. J Biol Chem. 2005;280:7511–8.
[152] Perreault M,Marette A.Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med. 2001;7:1138–43.
[153] Carvalho-Filho MA,Ueno M,Carvalheira JB,etal.Targeted disruption of iNOS prevents LPS-induced S-nitrosation of IRbeta/IRS-1 and Akt and insulin resistance in muscle of mice. Am J Physiol Endocrinol Metab. 2006;291:E476–82.
[154]Carvalho-Filho MA, S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt:a novel mechanism of insulin resistance. Diabetes. 2005;54:959–67.
[155] Schottelius AJ,Mayo MW,Sartor RB,etal.Jr Interleukin-10 signaling blocks inhibitor of kappaB kinase activity and nuclear factor kappaB DNA binding.J Biol Chem. 1999;274:31868–74.
[156] van Exel E,Gussekloo J,de Craen AJ,etal.Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study. Diabetes. 2002;51:1088–92.
[157] Kim HJ, Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes. 2004;53:1060–7.
[158] Lumeng CN,Bodzin JL,Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117:175–84.
[159] Senn JJ,KloverPJ, Nowak IA,Interleukin induces cellular insulin resistance in hepatocytes.Diabetes, 2002, 51: 3391-9.
[160] Kopp HP, Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol. 2003;23:1042–7.
[161] Fontana L,Eagon JC,Trujillo ME,etal.Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010–3.
[162] Klover PJ,Clementi AH,Mooney RA.Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology. 2005;146:3417–27.
[163] Wallenius V,Interleukin-6-deficient mice develop mature-onset obesity.Nat Med. 2002;8:75–9.
[164] Di Gregorio GB,Hensley L, Lu T, etal.Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am J Physiol Endocrinol Metab. 2004;287:E182–7.
[165] Flier JS.Obesity wars: molecular progress confronts an expanding epidemic.Cell. 2004;116:337–50.
[166] Wernstedt I, Edgley A, Berndtsson A,etal. Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice. Am J Physiol Regul Integr Comp Physiol. 2006;291:R551–7.
[167] Febbraio MA.gp130 receptor ligands as potential therapeutic targets for obesity. J Clin Invest. 2007;117:841–9.
[168]Marina Cardellini MD.Lucia Perego PHD,Monica D’Adamo MD,etal.C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance.J Diabetes Care 28:2007-2012,2005.
[169] Dinarello, CA. Blocking IL-1 in systemic inflammation. J Exp Med. 2005;201:1355–9.
[170] Matsuki T,Horai R, Sudo K,etal.IL-1 plays an important role in lipid metabolism by regulating insulin levels under physiological conditions. J Exp Med. 2003;198:877–88.
[171]Spranger J,Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes. 2003;52:812–7.
[172] Jager J,GremeauxT,Cormont M,Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007;148:241–51.
[173] Zerr KJ,Furnary AP,Grunkemeier GL,etal.Glucose Control Lowers the Risk of Wound Infection in Diabetics afterOpen-Heart Operation[J]. Ann Thorac Surg 1997,63:356-361.
[174] Rassias A,Marrin CAS,Arruda J,etal. Insulin Infusion Improves Neutrophil Function in Diabetic Cardiac Surgery Patients[J]. Anesth Analg. 1999,88:1011-1016.
[175] Rassias A,Givan A,Marrin CA S,etal.Insulin Increases Neutrophil Count and Phagocytic Capacity after Cardiac Surgery[J].Anesth Analg. 2002,94:1113-1119.
[176] Lazar HL,Chipkin S,Philippides G,etal. Glucose insulin-potassium solutions improve outcomes in diabetics who have coronary artery operations[J].Ann Thorac Surg. 2000,70:145-150.
[177] Ramanathan T,Shirota K,Morita S,etal. Glucose-insulin-potassium solution improves left ventricular mechanics in diabetes[J]. Ann Thorc Surg. 2002,73:582-587.
[178] Lell WA,Neilson VG,McGiffin,DC,etal.Glucose-insulin-potassium infusion for myocardial protection during off-pump coronary artery surgery[J].Ann Thorac Surg. 2002,73:1246-1251.
[179] Thorell A, Nygren J,Ljungqvist O,etal. Insulin resistance: a marker of surgical stress[J]. Curr Opin NutrMetab Care,1999, 2:69-78.
[180] Silistreli E,CatalyurekH,SariosmanoN,etal.Effectson the Endocrine System of Pulsatile and Nonpulsatile in Heart Surgery[J].Asian Cardiovasc Thorac Ann,1999,7:18-22.
[181]王占科,许霖水,吴贵喜.TNF-α与烧伤后胰岛素抵抗相关性的研究[J].第三军医大学学报,1997,19:310-312.
[182]Friehs I,Stamm C,Hung C D,et al. Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts[J].Ann Thorac Surg. 2001,72:1650-1656. .