短时间被动冷却通过诱导热休克蛋白和限制促炎细胞因子的诱导来保护肝切除大鼠。
Short passive cooling protects rats during hepatectomy by inducing heat shock proteins and limiting the induction of pro-inflammatory cytokines.
机构信息
Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California 94143-0648, USA.
出版信息
J Surg Res. 2010 Jan;158(1):43-52. doi: 10.1016/j.jss.2008.08.030.
BACKGROUND
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.
METHODS
The left and median lobes of male rats were exposed to 75 min of ischemia under either normothermic (37 degrees C) or mildly hypothermic (34 degrees 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.
RESULTS
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-alpha (TNF-alpha) 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).
CONCLUSION
We demonstrated in a clinically relevant model of hepatic ischemia/reperfusion that mild hypothermia significantly reduces hepatic injury and improves survival.
背景
手术过程中肝脏的长时间热缺血仍然是一个重大问题，特别是在肝切除和剩余肝质量减少的情况下。本研究的目的是评估在常温（37°C）或轻度低温（34°C）条件下暴露于环境条件下导致的被动冷却对大鼠热缺血后肝切除时肝损伤的影响。
方法
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 75 分钟的缺血状态下。75 分钟缺血后，切除右叶，使动物只剩下剩余的缺血叶。动物可以无限期存活或在再灌注后 4 小时处死，以确定损伤和炎症基因表达。
结果
轻度低温组大鼠在 24 小时时的存活率明显高于常温组。短暂的被动冷却时间与缺血事件相同，显著增加了肝脏对缺血/再灌注的热休克蛋白 70 和 32 的诱导（均为常温的 3 倍，P<0.05），而显著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。与常温动物相比，被动冷却组的肝损伤生化标志物明显较低：天冬氨酸氨基转移酶（AST）血清浓度为 9277+/-3461IU/L 与 15106+/-4104IU/L（P<0.01），丙氨酸氨基转移酶（ALT）水平为 5986+/-2246IU/L 与 9429+/-3643IU/L（P<0.01）。
结论
我们在一个与临床相关的肝缺血/再灌注模型中证明，轻度低温可显著减轻肝损伤并提高存活率。
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