Department of Emergency Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea.
J Surg Res. 2013 May 1;181(1):114-20. doi: 10.1016/j.jss.2012.05.045. Epub 2012 Jun 1.
Therapeutic hypothermia has been proposed to protect organs in some diseases. However, the effect of therapeutic hypothermia on liver injury in sepsis is unknown. The aim of this study was to evaluate the effects of therapeutic hypothermia on liver injury in sepsis.
Male Sprague-Dawley rats underwent cecal ligation and incision (CLI). We randomly allocated rats into one of two groups 1 h after CLI: hypothermia (HT) and normothermia (NT). In the HT group, body temperature decreased to 32°C ± 0.5°C and was maintained 4 h, followed by rewarming to 37°C for 2 h. In the NT group, body temperature was maintained at 37°C ± 0.5°C throughout the experimental periods. At 7 h after CLI, we harvested blood and liver tissues and measured serum alanine aminotransferase and the histological liver injury score. We performed immunohistochemistry for cleaved caspase-3 and evaluated phosphorylation of Akt, GSK-3β and Bad with the Western blot assay.
Serum alanine aminotransferase was significantly lower in the HT group than in the NT group (57.0 ± 6.0 IU/L versus 192.5 ± 92.5 IU/L; P = 0.028). The histological liver injury score was also significantly lower in the HT group than in the NT group (2.9 ± 0.5 versus 5.4 ± 0.6; P = 0.016). Phosphorylation of Akt, GSK-3β, and Bad was significantly increased in the HT group compared with the NT group (P < 0.001, P = 0.007, and P = 0.001, respectively). Hypothermia significantly mitigated expression of cleaved caspase-3 compared with the NT group (P = 0.032).
Therapeutic hypothermia attenuated liver injury in a polymicrobial sepsis model of rats by enhancing the Akt signaling pathway and decreasing apoptosis.
在某些疾病中，已经提出了治疗性低温以保护器官。然而，治疗性低温对脓毒症肝损伤的影响尚不清楚。本研究旨在评估治疗性低温对脓毒症肝损伤的影响。
雄性 Sprague-Dawley 大鼠接受盲肠结扎和切开术（CLI）。在 CLI 后 1 小时，我们将大鼠随机分配到两组之一：低温组（HT）和常温组（NT）。在 HT 组中，体温降至 32°C±0.5°C 并维持 4 小时，随后再升温至 37°C 2 小时。在 NT 组中，体温在整个实验期间保持在 37°C±0.5°C。在 CLI 后 7 小时，我们采集血液和肝组织，测量血清丙氨酸氨基转移酶和肝组织损伤评分。我们通过免疫组织化学检测 cleaved caspase-3，并通过 Western blot 检测 Akt、GSK-3β 和 Bad 的磷酸化。
与 NT 组相比，HT 组血清丙氨酸氨基转移酶显著降低（57.0±6.0 IU/L 与 192.5±92.5 IU/L；P=0.028）。HT 组肝组织损伤评分也明显低于 NT 组（2.9±0.5 与 5.4±0.6；P=0.016）。与 NT 组相比，HT 组 Akt、GSK-3β 和 Bad 的磷酸化明显增加（P<0.001，P=0.007 和 P=0.001）。与 NT 组相比，低温显著减轻了 cleaved caspase-3 的表达（P=0.032）。
在大鼠多微生物脓毒症模型中，治疗性低温通过增强 Akt 信号通路和减少细胞凋亡来减轻肝损伤。
