Department of Anesthesiology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Department of Anesthesiology, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan.
J Anesth. 2019 Jun;33(3):390-398. doi: 10.1007/s00540-019-02642-4. Epub 2019 May 3.
Ischemia-reperfusion (IR) injury is inevitable after liver transplantation and liver resection with inflow occlusion. Sevoflurane has been widely used during hepatobiliary surgery and was reported to exhibit preconditioning (PreC) properties against hepatic IR injury; however, its postconditioning (PostC) properties remain unknown. This study examined whether a clinically applicable dose of sevoflurane has PostC and PreC properties against hepatic IR injury and roles of heme oxygenase-1 (HO-1).
Warm ischemia was induced in male Wistar rats, excluding the sham group, for 1 h, followed by 3 h of reperfusion. Group C received propofol from 60 min before ischemia until the end of the experimental procedure. In the SPreC and SPostC groups, propofol was replaced by 2.5% sevoflurane for 30 min from 35 min before ischemia in the SPreC group and for 30 min from 5 min before reperfusion in the SPostC group. The SPreC+Z and SPostC+Z groups received a HO-1 inhibitor, zinc protoporphyrin (Znpp), 60 min before ischemia, and sevoflurane PreC and PostC were induced.
Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, and histological damage scores in the SPreC and SPostC groups were significantly lower than those in group C. Inhibiting HO-1 with Znpp partially blocked these protective effects of sevoflurane. Sevoflurane PreC and PostC significantly increased the number of HO-1-positive Kupffer cells in comparison with group C, and Znpp prevented sevoflurane-induced HO-1 expression.
PostC and PreC by sevoflurane at a clinically applicable dose have equally protective effects against hepatic IR injury by increasing HO-1 expression.
肝移植和入肝血流阻断肝切除后必然发生缺血再灌注（IR）损伤。七氟醚在肝胆外科中被广泛应用，并被报道具有肝IR 损伤的预处理（PreC）特性；然而，其后处理（PostC）特性尚不清楚。本研究旨在探讨临床可应用剂量的七氟醚对肝 IR 损伤是否具有 PostC 和 PreC 特性，以及血红素加氧酶-1（HO-1）的作用。
雄性 Wistar 大鼠除假手术组外，热缺血 1 h，再灌注 3 h。C 组从缺血前 60 min 至实验结束给予异丙酚。在 SPreC 和 SPostC 组中，SPreC 组从缺血前 35 min 开始，SPostC 组从再灌注前 5 min 开始，用 2.5%七氟醚替代异丙酚 30 min。SPreC+Z 和 SPostC+Z 组在缺血前 60 min 给予 HO-1 抑制剂锌原卟啉（Znpp），并诱导七氟醚 PreC 和 PostC。
SPreC 和 SPostC 组血清天冬氨酸转氨酶、丙氨酸转氨酶和乳酸脱氢酶水平及组织学损伤评分明显低于 C 组。用 Znpp 抑制 HO-1 部分阻断了七氟醚的这些保护作用。与 C 组相比，七氟醚 PreC 和 PostC 显著增加了 HO-1 阳性枯否细胞的数量，而 Znpp 阻止了七氟醚诱导的 HO-1 表达。
临床可应用剂量的七氟醚 PreC 和 PostC 同样具有保护作用，可通过增加 HO-1 表达来减轻肝 IR 损伤。
