Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis
Effect of ischaemic preconditioning on hepatic oxygenation, microcirculation and function in a rat model of moderate hepatic steatosis
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DOI：
10.1042/cs20040130
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发表时间：
2005-01-01
期刊：
影响因子：
6
通讯作者：
Seifalian, AM
中科院分区：
文献类型：
--
作者：
Koti, RS;Yang, WX;Seifalian, AM
IPC（缺血预处理）可以保护脂肪肝，特别容易受到 I/R（缺血/再灌注）损伤。用高胆固醇 (2%) 饮食诱导 Sprague-Dawley 大鼠肝脂肪变性 12 周，然后对大鼠进行 I/R（缺血/再灌注；45 分钟脑叶缺血，然后 2 小时再灌注）。将大鼠分为三个研究组（每组 n = 6），在 I/R 之前接受：（i）单独的假剖腹手术，（ii）I/R，和（iii）IPC（5 分钟缺血，然后 10 分钟再灌注）。分别用近红外光谱和激光多普勒血流计测量肝细胞外和细胞内氧合以及 HM（肝微循环）。测量血浆肝酶和肝组织 ATP 作为肝损伤的标志物。组织学显示肝脏中度脂肪变性。再灌注 2 小时结束时，I/R 显着降低细胞外和细胞内氧合，同时 HM 恢复失败（基线的 21.1 +/- 14.4%；与假手术动物相比，P < 0.001）。 IPC 增加细胞内氧合（细胞色素氧化酶铜中心的氧化还原状态；与仅接受 I/R 的大鼠相比，P < 0.05）和 HM 中的流量（基线的 70.9 +/- 17.1%；与仅接受 I/R 的大鼠相比，P < 0.001）。与单独 I/R 损伤相比，IPC 的肝细胞损伤显着减轻（丙氨酸转氨酶，分别为 474.8 +/- 122.3 与 5436.3 +/- 984.7 单位/升相比；P < 0.01；天冬氨酸转氨酶，分别为 630.8 +/- 76.9 与 3166.3 +/- 379.6 单位/升相比；P < 0.01] 总之，IPC 对中度脂肪变性肝脏的 I/R 损伤具有保肝作用，这些数据可能对肝脏手术和移植具有重要的临床意义。
IPC (ischaemic preconditioning) may protect the steatotic liver, which is particularly susceptible to I/R (ischaemia/reperfusion) injury. Hepatic steatosis was induced in Sprague-Dawley rats with a high-cholesterol (2%) diet for 12 weeks after which rats were subjected to I/R (ischaemia/reperfusion; 45 min of lobar ischaemia followed by 2 h of reperfusion). Rats were divided into three study groups (n = 6 each) receiving: (i) sham laparotomy alone, (ii) I/R, and (iii) IPC (5 min of ischaemia. followed by 10 min of reperfusion) before I/R. Hepatic extra- and intra-cellular oxygenation and HM (hepatic microcirculation) were measured with near-infrared spectroscopy and laser Doppler flowmetry respectively. Plasma liver enzymes and hepatic tissue ATP were measured as markers of liver injury. Histology showed moderate-grade steatosis in the livers. At the end of 2 h of reperfusion, I/R significantly decreased extra- and intra-cellular oxygenation concomitant with a failure of recovery of HM (21.1 +/- 14.4% of baseline; P < 0.001 compared with sham animals). IPC increased intracellular oxygenation (redox state of the copper centre of cytochrome oxidase; P < 0.05 compared with rats receiving I/R alone) and flow in HM (70.9 +/- 17.1% of baseline; P < 0.001 compared with rats receiving I/R alone). Hepatocellular injury was significantly reduced with IPC compared with I/R injury alone (alanine aminotransferase, 474.8 +/- 122.3 compared with 5436.3 +/- 984.7 units/l respectively; P < 0.01; aspartate aminotransferase, 630.8 +/- 76.9 compared with 3166.3 +/- 379.6 units/l respectively; P < 0.01]. In conclusion, IPC has a hepatoprotective effect against I/R injury in livers with moderate steatosis. These data may have important clinical implications in liver surgery and transplantation.