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Title:: Effects of intensive insulin therapy on inflammatory mediators in children undergoing cardiac surgery with cardiopulmonary bypass

作者:: 豆亚伟; 崔勤; 马超; 赵荣; 郑霄; 第四军医大学西京医院心血管外科,陕西西安 710032

Author(s):: DOU Yawei; CUI Qin; MA Chao; ZHAO Rong; ZHENG Xiao; Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, Chin

关键词:: 体外循环; 强化胰岛素治疗; 炎症介质; 胰岛素受体; 核转录因子κB

Keywords:: cardiopulmonary bypass; intensive insulin therapy; inflammatory mediators; insulin receptor; nuclear factorkappaB

分类号:: R587.29

DOI:: -

文献标识码:: A

摘要:: 目的探讨强化胰岛素治疗对儿童体外循环（CPB）心脏手术炎症介质的影响，及其减轻CPB术后全身炎症反应的机制。方法 20例CPB下心脏手术儿童随机分为常规治疗组（RT组，n=10）和强化胰岛素治疗组（IT组，n=10）。IT组患儿术中血糖控制在44～100 mmol/L（700～1 800 mg/L），术后控制在44～83 mmol/L（700～1 500 mg/L）；RT组患者血糖变化不作处理。分别于术前、麻醉诱导、CPB开始后及CPB结束0，4，12，24和48 h测定两组患儿的血浆胰岛素、白介素-1β(IL-1β)、白介素-6（IL-6）、白介素-10(IL-10)和肿瘤坏死因子α（TNF-α）水平。建立CPB前和CPB结束时在右心耳切口缘取心肌,Western blot测定心肌胰岛素受体（InsR）、核转录因子κB(NF-κBp65)表达。结果两组胰岛素水平在CPB开始后上升，于CPB结束时达高峰，随后下降；IT组胰岛素水平从CPB后显著高于RT组(P<0.05,P<0.01)。两组TNFα和IL-1β、IL-6水平在CPB开始后上升，CPB后3 h达高峰，随后下降；IT组TNF-α和IL-1β、IL-6水平从CPB后开始显著低于RT组(P<0.05，P<0.01)。两组IL-10水平在CPB结束时上升，于CPB 12 h达高峰，随后下降；两组IL-10水平无显著性差异（P>0.05）。CPB后两组InsR表达与CPB前相比均显著增加（P<0.05），强化胰岛素治疗CPB后InsR表达较RT显著增加（P<0.05）。两组CPB后NF-κBp65表达与未干预组相比均显著增加（P<0.05）；但CPB后两组间NFκBp65表达无显著差异。结论强化胰岛素治疗上调胰岛素受体的表达，改善胰岛素抵抗状态，减弱 TNF-α和IL1β、IL-6的表达，起到调节全身炎症反应的作用。

Abstract:: AIM To investigate the effects and mechanisms of intensive insulin therapy on inflammatory mediators in children undergoing cardiac surgery with cardiopulmonary bypass. METHODS A total of 20 children were randomly assigned to routine therapy (RT) group and intensive insulin therapy (IT) group, with 10 children in each group. The blood glucose levels during surgery were maintained at 44-10 mmol/L (700-1 800 mg/L) and at 44-83 mmol/L（700-1 500 mg/L）after surgery in IT group, whereas the patients in RT group received no treatment of controlling glucose levels. The levels of insulin, IL-1β, IL-6, IL-10 and TNF-α in both groups were respectively measured before surgical anesthesia, after the initiation of cardiopulmonary bypass (CPB), and 0 h, 4 h, 12 h, 24 h and 48 h after the termination of CPB. InsR and NFκBp65 expression in cardiomyocytes pre and postCPB was analyzed by Western blot. RESULTS In both groups, plasma insulin concentration increased after the initiation of CPB, reached the peak 0 h after the termination of CPB, and then began to decrease. Compared with those in RT group, the levels at different time points after the termination of CPB were higher (P<005, P<0.01) in IT group. In both groups, TNF-α, IL-1β and IL-6 levels increased after the initiation of CPB, reached the peak 3 h after the termination of CPB and then began to decrease. Compared with those in RT group, the levels at different time points after the termination of CPB were lower in IT group (P<0.05, P<0.01). In both groups, IL-10 was increased after the termination of CPB, reached the peak 12 h after the termination of CPB and then began to decrease. There was no significant difference between the two groups in IL-10 levels. InsR expression in cardiomyocytes in both groups increased postCPB (compared with that preCPB， P<0.05) and after intensive insulin therapy it was significantly higher postCPB (compared with that in RT group， P<0.05). In both groups, NF-κBp65 expression in cardiomyocytes increased postCPB (compared with that preCPB， P<0.05)，but no significant difference was found between the two groups postCPB. CONCLUSION Intensive insulin therapy increases InsR expression in cardiomyocytes during pediatric cardiovascular surgery and improves insulin resistance and reduces TNF-α, IL-1β and IL-6 levels. Our study suggests that intensive insulin therapy can adjust systemic inflammatory reaction.

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强化胰岛素治疗对儿童体外循环心脏手术炎症介质的影响(PDF)

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