Iwanami K, Takeyoshi I, Ohwada S, Kobayashi J, Kawashima Y, Aiba M, Matsumoto K, Morishita Y
Second Department of Surgery, Gunma University School of Medicine, Japan.
Surgery. 1999 Nov;126(5):908-17.
In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and it sometimes causes liver failure. This study was designed to evaluate the effect of Lazaroid U-74389G (LAZ-G), which inhibits iron-dependent lipid peroxidation, on ischemia-reperfusion injury during liver resection in dogs.
The experiment animals were divided into 2 groups. The control group was subjected to 60 minutes of warm ischemia by partial inflow occlusion. The LAZ-G-treated group received LAZ-G before ischemia and then underwent liver ischemia. After reperfusion, the nonischemic lobes were resected, and the remnant liver function was evaluated.
The LAZ-G-treated group showed a significantly improved animal survival rate. Biochemical analysis and morphologic evaluation by electron microscopy suggest that LAZ-G pretreatment protects both hepatic parenchymal cells and sinusoidal endothelial cells from ischemia-reperfusion injury. Expression of IL-1 beta messenger RNA in hepatic venous blood was measured by a reverse transcriptase-polymerase chain reaction; it was shown to be inhibited in the LAZ-G-treated group after reperfusion. This suggests that LAZ-G decreases the activation of proinflammatory cytokine expression.
Lazaroid U-74389G ameliorates ischemia-reperfusion injury caused by Pringle's procedure during extensive liver resection. This agent may therefore be clinically applicable for extended liver surgery involving vascular isolation.
在肝脏手术中，门静脉三联征完全阻断（普林格尔手术）被广泛应用，但有时会导致肝衰竭。本研究旨在评估抑制铁依赖性脂质过氧化的拉扎罗类药物U - 74389G（LAZ - G）对犬肝切除术中缺血再灌注损伤的影响。
将实验动物分为两组。对照组通过部分血流阻断进行60分钟的热缺血。LAZ - G治疗组在缺血前给予LAZ - G，然后进行肝脏缺血。再灌注后，切除非缺血叶，并评估残余肝功能。
LAZ - G治疗组动物存活率显著提高。生化分析和电子显微镜形态学评估表明，LAZ - G预处理可保护肝实质细胞和肝血窦内皮细胞免受缺血再灌注损伤。通过逆转录聚合酶链反应测定肝静脉血中IL - 1β信使核糖核酸的表达；结果显示再灌注后LAZ - G治疗组该表达受到抑制。这表明LAZ - G可降低促炎细胞因子表达的激活。
拉扎罗类药物U - 74389G可改善广泛肝切除术中普林格尔手术引起的缺血再灌注损伤。因此，该药物可能在涉及血管隔离的扩大肝手术中具有临床应用价值。
