【作者】 高胜特；

【导师】 方刚； 李德；

【作者基本信息】 宁夏医科大学 ， 外科学， 2010， 硕士

【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。更多还原

【Abstract】 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 correlation6. Proinflammatory cytokine and insulin resistance is exitting a positive correlation更多还原