Braun Sebastian, Plitzko Gabriel, Bicknell Leonie, van Caster Patrick, Schulz Jan, Barthuber Carmen, Preckel Benedikt, Pannen Benedikt H, Bauer Inge
*Department of Anesthesiology, University Hospital Düsseldorf, Düsseldorf, Germany; †Department of Visceral Surgery, University of Bern, Switzerland; ‡Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; §Institute of Clinical Chemistry and Laboratory Diagnostics, University Hospital Düsseldorf, Düsseldorf, Germany; and ∥Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, the Netherlands.
Shock. 2014 May;41(5):413-9. doi: 10.1097/SHK.0000000000000125.
Preconditioning with noble gases serves as an effective strategy to diminish tissue injury in different organs. The aim of this study was to investigate the influence of pretreatment with the nonanesthetic noble gas helium on hepatic injury after warm ischemia and reperfusion (IR) in comparison to ischemic preconditioning (IPC). Anesthetized and ventilated rats were randomized into six groups (n = 8/group): sham: after laparotomy, the portal triad was exposed without clamping; IPC was performed with 10 min of partial liver ischemia and 10 min of reperfusion; HePC: three cycles of 5 min with inhalation of helium 70 vol% and intermittent washout; IR: 45 min of ischemia followed by 240 min of reperfusion; IPC-IR: IPC followed by hepatic IR; HePC-IR: pretreatment with helium 70 vol% followed by hepatic IR. Hepatic injury was evaluated by measurement of serum enzymes aspartate aminotransferase and alanine aminotransferase. Hepatic mRNA expression and serum levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were measured with real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Myeloperoxidase in liver tissue was assessed spectrophotometrically as a marker of neutrophil accumulation. mRNA levels of heme oxygenase 1 in liver tissue were assessed to investigate a protein of the most abundant protective system in the liver. Aspartate aminotransferase and alanine aminotransferase serum activities increased after hepatic IR (sham vs. IR; P < 0.05). The serum levels of liver enzymes after IR were significantly diminished with IPC (P < 0.05), whereas helium pretreatment had no effect. mRNA expression of TNF-α increased in all groups except IPC-IR compared with sham, whereas mRNA expression of IL-10 increased only after helium pretreatment. Serum levels of IL-10 were not affected by any intervention, whereas serum levels of TNF-α and liver myeloperoxidase were increased after IR, but not after HePC-IR. In conclusion, pretreatment with inhaled helium does not attenuate hepatic injury after warm IR of the liver, although there is evidence for a modulation of the inflammatory response.
用惰性气体进行预处理是减轻不同器官组织损伤的一种有效策略。本研究的目的是，与缺血预处理（IPC）相比，研究用非麻醉性惰性气体氦进行预处理对肝脏热缺血再灌注（IR）后肝损伤的影响。将麻醉并通气的大鼠随机分为六组（每组n = 8）：假手术组：剖腹术后，暴露门静脉三联体但不夹闭；IPC组：进行10分钟的部分肝脏缺血和10分钟的再灌注；氦预处理组（HePC）：吸入70%体积分数氦气5分钟，间歇冲洗，共三个循环；IR组：缺血45分钟，随后再灌注240分钟；IPC-IR组：IPC后进行肝脏IR；HePC-IR组：用70%体积分数氦气预处理后进行肝脏IR。通过测定血清天冬氨酸转氨酶和丙氨酸转氨酶评估肝损伤。分别用实时定量聚合酶链反应和酶联免疫吸附测定法测定肝组织中肿瘤坏死因子α（TNF-α）和白细胞介素10（IL-10）的mRNA表达及血清水平。用分光光度法评估肝组织中的髓过氧化物酶作为中性粒细胞聚集的标志物。评估肝组织中血红素加氧酶1的mRNA水平以研究肝脏中最丰富的保护系统的一种蛋白质。肝脏IR后，天冬氨酸转氨酶和丙氨酸转氨酶血清活性升高（假手术组与IR组比较；P < 0.05）。IPC可使IR后的肝酶血清水平显著降低（P < 0.05），而氦预处理无作用。与假手术组相比，除IPC-IR组外，所有组中TNF-α的mRNA表达均增加，而IL-10的mRNA表达仅在氦预处理后增加。IL-10的血清水平不受任何干预影响，而TNF-α的血清水平和肝脏髓过氧化物酶在IR后升高，但在HePC-IR后未升高。总之，吸入氦预处理不能减轻肝脏热IR后的肝损伤，尽管有证据表明炎症反应受到了调节。
