Short passive cooling protects rats during hepatectomy by inducing heat shock proteins and limiting the induction of pro-inflammatory cytokines.

Short passive cooling protects rats during hepatectomy by inducing heat shock proteins and limiting the induction of pro-inflammatory cytokines.
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DOI:
10.1016/j.jss.2008.08.030
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发表时间:
2010-01
期刊:
The Journal of surgical research
影响因子:
--
通讯作者:
Maher JJ
Maher JJ
中科院分区:
其他
文献类型:
--
作者:
Niemann CU;Xu F;Choi S;Behrends M;Park Y;Hirose R;Maher JJ

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手术期间长时间的肝脏热缺血仍然是一个重大问题,特别是在肝切除和剩余肝脏质量减少的情况下。本研究的目的是评估暴露于环境条件引起的被动冷却对大鼠热缺血随后肝切除期间肝损伤的影响。将雄性大鼠的左叶和中叶在常温(37°C)或轻度低温(34°C)条件下暴露于缺血75分钟。缺血75分钟后,切除右肺叶,只留下剩余的缺血肺叶。允许动物无限期存活或在再灌注后4小时处死以测定损伤和炎症基因表达。 24 小时时,轻度低温大鼠的存活率明显高于常温大鼠。缺血事件期间的短暂被动冷却显着增加了肝脏对缺血/再灌注反应的热休克蛋白 70 和 32 的诱导(均为正常体温的 3 倍,P < 0.05),同时显着降低了肝脏中肿瘤坏死因子-α (TNF-α) 和巨噬细胞炎症蛋白 2 (MIP-2) 的诱导。被动降温组的肝损伤生化标志物显着低于常温动物:天冬氨酸转氨酶(AST)血清浓度分别为9277±3461IU/L和15106±4104IU/L(P<0.01),丙氨酸转氨酶(ALT)水平为5986±2246IU/L和9429±3643IU/L。 (P<0.01)。我们在临床相关的肝缺血/再灌注模型中证明,轻度低温可显着减少肝损伤并提高生存率。
Prolonged hepatic warm ischemia during surgery remains a significant problem, particularly in the setting of liver resection and reduced remaining liver mass. The goal of the present study is to evaluate the effect of passive cooling caused by exposure to ambient conditions on hepatic injury in rats during warm ischemia followed by hepatectomy. The left and median lobes of male rats were exposed to 75 min of ischemia under either normothermic (37°C) or mildly hypothermic (34°C) conditions. After 75 min of ischemia, the right lobe was resected, leaving the animal with only the remaining ischemic lobes. Animals were allowed to survive indefinitely or sacrificed at 4 h after reperfusion for determination of injury and inflammatory gene expression. Survival was already markedly higher in mildly hypothermic rats than normothermic rats at 24 h. Short passive cooling for the time course of the ischemic event significantly increased the hepatic induction of heat shock proteins 70 and 32 (both 3-fold versus normothermia, P < 0.05) in response to ischemia/reperfusion whereas it significantly decreased the induction of tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) in the liver. Biochemical markers of hepatic injury were significantly lower in the passive cooling group than in normothermic animals: aspartate aminotransferase (AST) serum concentrations were 9277 ± 3461IU/L versus 15106 ± 4104IU/L (P<0.01), and alanine aminotransferase (ALT) levels 5986 ± 2246IU/L versus 9429 ± 3643IU/L (P<0.01). We demonstrated in a clinically relevant model of hepatic ischemia/reperfusion that mild hypothermia significantly reduces hepatic injury and improves survival.
DOI: 10.1097/00007890-200207150-00017
发表时间: 2002-07-15
期刊: TRANSPLANTATION
影响因子: 6.2
作者:
Coito, AJ;Buelow, R;Kupiec-Weglinski, JW
通讯作者: Kupiec-Weglinski, JW
DOI: 10.1016/s0039-6060(03)00125-9
发表时间: 2003-11-01
期刊: SURGERY
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DOI: 10.1097/01.sla.0000154259.73060.f1
发表时间: 2005-03-01
期刊: ANNALS OF SURGERY
影响因子: 9
作者:
Choi, S;Noh, J;Nienmann, CU
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DOI: 10.1152/ajpgi.00422.2005
发表时间: 2006-04-01
影响因子: 4.5
作者:
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DOI: 10.1097/00024382-200206000-00014
发表时间: 2002-06-01
期刊: SHOCK
影响因子: 3.1
作者:
Kentner, R;Rollwagen, FM;Tisherman, SA
通讯作者: Tisherman, SA