Kaya Yavuz, Coskun Teoman, Aral Erinc, Erkasap Nilüfer, Var Ahmet
Department of Surgery, Celal Bayar University, Faculty of Medicine, Manisa, Turkey.
Hepatogastroenterology. 2003 May-Jun;50(51):651-5.
BACKGROUND/AIMS: It has been shown that hepatic blood inflow occlusion impairs liver regeneration. Our aim in this study was to investigate the effect of trimetazidine, known as an anti-ischemic and anti-oxidant agent, on liver regeneration after hepatic blood inflow occlusion.
Sprague-Dawley rats were randomized into three groups. Rats in group 1 underwent 65% hepatectomy. Rats in group 2 and 3 were subjected to 15 minutes of hepatic blood inflow occlusion during 65% hepatectomy. Rats were treated with saline (in group 1 and 2) or trimetazidine (in group 3) 30 minutes before operation. Serum level of aspartate transaminase, wet to dry liver weight ratio, and liver injury score in light microscopy were studied for the evaluation of liver injury. Liver regeneration was evaluated by PCNA-labeling index (the percentage of hepatocytes staining for proliferating cell nuclear antigen), mitotic index (the percentage of mitotic hepatocytes), and liver regeneration rate (the percentage of initial liver weight).
Rats in group 2 and 3 had significantly higher serum aspartate transaminase level, wet to dry liver weight ratio and injury score than those in group 1 on day 1 posthepatectomy. Except for serum aspartate transaminase level on day 4, these parameters were significantly higher in group 2 than in group 1 and 3 on day 1 and 4. PCNA-labeling index and mitotic index were significantly less in group 2 and 3 than in group 1 on day 1. In contrast to liver regeneration rate, both indices in group 2 were significantly less than those in group 3 on day 1. There were no differences in regeneration parameters between the groups on day 4. Survival rate was significantly higher in group 3 than in group 2.
Fifteen minutes of hepatic blood inflow occlusion caused an injury in the remnant liver, impaired liver regeneration, and decreased survival rate after partial hepatectomy. However, pretreatment with trimetazidine reduced liver injury, and improved liver regeneration and survival rate. For situations where hepatic blood inflow occlusion is planned in major liver resection, trimetazidine pretreatment would be useful strategy to improve postoperative outcome.
背景/目的：已有研究表明，肝血流阻断会损害肝脏再生。本研究的目的是探讨曲美他嗪（一种已知的抗缺血和抗氧化剂）对肝血流阻断后肝脏再生的影响。
将Sprague-Dawley大鼠随机分为三组。第1组大鼠接受65%肝切除术。第2组和第3组大鼠在65%肝切除术中接受15分钟的肝血流阻断。术前30分钟，第1组和第2组大鼠用生理盐水处理，第3组大鼠用曲美他嗪处理。通过检测血清天冬氨酸转氨酶水平、肝湿重与干重比值以及光镜下肝损伤评分来评估肝损伤。通过增殖细胞核抗原（PCNA）标记指数（增殖细胞核抗原染色的肝细胞百分比）、有丝分裂指数（有丝分裂肝细胞百分比）和肝脏再生率（初始肝脏重量百分比）评估肝脏再生。
肝切除术后第1天，第２组和第３组大鼠的血清天冬氨酸转氨酶水平、肝湿重与干重比值及损伤评分显著高于第1组。除术后第4天的血清天冬氨酸转氨酶水平外，术后第1天和第4天，第2组的这些参数显著高于第1组和第3组。术后第1天，第2组和第3组的PCNA标记指数和有丝分裂指数显著低于第1组。与肝脏再生率相反，术后第1天第2组的这两个指数均显著低于第3组。术后第4天，各组间再生参数无差异。第3组的生存率显著高于第2组。
15分钟的肝血流阻断会导致残余肝脏损伤，损害肝脏再生，并降低部分肝切除术后的生存率。然而，曲美他嗪预处理可减轻肝损伤，改善肝脏再生和生存率。对于计划在大肝切除术中进行肝血流阻断的情况，曲美他嗪预处理将是改善术后结局的有效策略。
