Ethanol potentiates the acute fatty infiltration of liver caused by burn injury: prevention by insulin treatment.
Ethanol potentiates the acute fatty infiltration of liver caused by burn injury: prevention by insulin treatment.
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DOI：
10.1097/bcr.0b013e3181a28df3
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Callaci JJ
中科院分区：
文献类型：
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作者：
Emanuele NV;Emanuele MA;Morgan MO;Sulo D;Yong S;Kovacs EJ;Himes RD;Callaci JJ
烧伤是危重疾病的重要且严重的表现。近 50% 因烧伤入院的患者循环中可检测到乙醇含量，这些患者的临床结果比未检测到循环乙醇的烧伤患者要差。我们在这里报告了一种临床相关肝损伤形式的数据，即在小鼠模型中微泡脂肪变性的发展，其中动物被给予乙醇或盐水，并受到烧伤或假伤。由于临床研究表明胰岛素可以更好地控制血糖，从而带来重大的临床益处，因此另一组烧伤乙醇的动物接受了胰岛素治疗。胰岛素显着降低受伤动物的血糖水平，与未接触乙醇或烧伤的动物的血糖水平没有什么不同。单次腹腔注射乙醇不足以升高血液丙氨酸氨基转移酶（ALT），而丙氨酸氨基转移酶是作为肝损伤指标来测量的。然而，烧伤导致 24 小时和 48 小时 ALT 显着升高，7 天后恢复至受伤前水平。胰岛素治疗完全阻止了 ALT 升高。单次注射乙醇不会引起微泡脂肪变性增加，但确实增强了烧伤在受伤后 24 小时内增加微泡脂肪变性的能力。烧伤引起的微泡脂肪变性在 48 小时时也出现增加，但在 7 天时已消退。胰岛素治疗可预防微泡脂肪变性的增加。因此，乙醇会增强烧伤引起急性肝损伤的能力，而胰岛素治疗完全可以预防这种情况。这些发现可能具有重大的临床意义，并表明该模型可能有助于研究肝损伤的机制以及胰岛素在这种情况下的作用机制（可能是多种机制）。
Burn injury is a significant and severe representation of critical illness. Nearly, 50% of patients admitted to hospitals for burn injuries have detectable levels of ethanol in their circulations and these patients have poorer clinical outcomes than burned individuals without measurable circulating ethanol. We report here data on a clinically relevant form of hepatic injury, the development of microvesicular steatosis, in a murine model wherein animals were either given ethanol or saline, and were subjected to burn or sham injury. Because better glycemic control with insulin has been shown in clinical studies to impart major clinical benefit, an additional group of burn ethanol animals were treated with insulin. Insulin significantly reduced blood glucose in injured animals to levels no different from those seen in animals that were neither ethanol exposed nor burned. A single intraperitoneal injection of ethanol was insufficient to raise blood alanine aminotransferase (ALT), measured as an index of liver injury. However, burn injury led to significant increases in ALT at 24 and 48 hours, which had returned to preinjury levels by 7 days. This ALT rise was completely prevented with insulin treatment. A single injection of ethanol did not evoke increased microvesicular steatosis but did potentiate the ability of burn to do so at 24 hours after injury. The burn induced increase in microvesicular steatosis was also seen at 48 hours, but had subsided by 7 days. The increased microvesicular steatosis was prevented by insulin therapy. Thus, ethanol potentiates the ability of burn to cause acute liver injury, which is completely preventable by insulin therapy. These findings may have substantial clinical significance and suggest this model may be useful for the study of the mechanisms of hepatic injury as well as the mechanisms, probably multiple, of insulin action in this setting.