Karaman Abdurrahman, Kirimlioglu Hale, Tas Erkan, Karadag Nese, Gülsul Cebrail, Fadillioglu Ersin, Demircan Mehmet
Department of Pediatric Surgery, Faculty of Medicine, Turgut Ozal Medical Center, Inonu University, Malatya, Turkey.
Pediatr Surg Int. 2010 Feb;26(2):219-226. doi: 10.1007/s00383-009-2529-1.
Partial hepatectomy (PH) can be an inevitable surgical therapy in some conditions, such as hepatic malignancies, trauma or partial liver transplantation. Its capacity for regeneration distinguishes the liver from other essential organs. Regeneration is a complex process involving growth factors, cytokines, transcription factors, hormones, and oxidative stress products. In the event of ineffective or total absent liver regeneration, the life threatening picture of acute liver failure may supervene. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and antiinflammatory agent against autoimmune disease, on hepatic regeneration after PH in Wistar Albino rats.
Thirty-five Wistar albino rats were divided into five groups: group 1, control; group 2, sham; group 3, drug control (was treated with leflunomide 10 mg/kg/d/i.g.); group 4, PH; group 5, PH + leflunomide. As for PH, approximately 70% of the rat liver was surgically removed under general anesthesia. On postoperative day 3, all rats were humanely killed. Catalase (CAT), superooxide dismutase (SOD) and myeloperoxidase (MPO) activities with malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were determined in remnant liver tissue. Inflammatory process and liver regeneration were evaluated with H&E and KI67, respectively.
The tissue levels of MDA, PC and MPO were lower in group 5 than levels in group 1. PH significantly decreased the enzymatic activity of CAT (p < 0.05) and SOD. This reduction was significantly improved by the treatment with leflunomide. Histopathologically the enhancement of the liver parenchymal regeneration in the group 5 was significantly greater than the group 4.
The findings imply that oxidative stress products play a preventive role in liver regeneration after PH and leflunomide ameliorates the regeneration probably by the radical scavenging and antioxidant activities.
在某些情况下，如肝恶性肿瘤、创伤或部分肝移植，部分肝切除术（PH）可能是不可避免的外科治疗方法。肝脏的再生能力使其有别于其他重要器官。再生是一个复杂的过程，涉及生长因子、细胞因子、转录因子、激素和氧化应激产物。如果肝脏再生无效或完全缺失，可能会出现危及生命的急性肝衰竭情况。在本研究中，我们研究了来氟米特（一种新型的用于治疗自身免疫性疾病的免疫抑制和抗炎药物）对Wistar白化大鼠PH后肝脏再生的影响。
35只Wistar白化大鼠分为五组：第1组为对照组；第2组为假手术组；第3组为药物对照组（接受10 mg/kg/d腹腔注射来氟米特治疗）；第4组为PH组；第5组为PH + 来氟米特组。对于PH组，在全身麻醉下手术切除约70%的大鼠肝脏。术后第3天，所有大鼠均被人道处死。测定残余肝组织中的过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和髓过氧化物酶（MPO）活性以及丙二醛（MDA）、一氧化氮和蛋白质羰基（PC）水平。分别用苏木精-伊红（H&E）染色和Ki67评估炎症过程和肝脏再生情况。
第5组的MDA、PC和MPO组织水平低于第1组。PH显著降低了CAT（p < 0.05）和SOD的酶活性。来氟米特治疗显著改善了这种降低。组织病理学上，第5组肝实质再生的增强明显大于第4组。
研究结果表明，氧化应激产物在PH后肝脏再生中起预防作用，来氟米特可能通过自由基清除和抗氧化活性改善肝脏再生。
