Trotta Mauricio de Rosa, Cajaiba Dandara Murad, Parra Osório Miguel, Dagli Maria Lúcia Zaidan, Hernandez-Blazquez Francisco Javier
1Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Toxicol Pathol. 2014;42(2):414-21. doi: 10.1177/0192623313486316. Epub 2013 Apr 24.
Liver resection is a suitable option for the treatment of certain hepatic conditions, particularly hepatocarcinomas, in patients with cirrhosis. However, this disease impairs liver regeneration, which increases the risk of liver failure and postoperative death. Supportive treatments for regeneration of the remaining liver may be useful for the recovery of these patients. We demonstrated that nutritional hepatotrophic factors (NHF) is an effective regenerative stimulus for cirrhotic livers in rats subjected to partial hepatectomy (PH). The rats with thioacetamide-induced cirrhosis were subjected to PH, and they were divided into 2 groups. One group received intraperitoneal administration of NHF, and the other group received saline solution. After 12 days, biometric data, collagen content, hepatocyte regeneration (proliferation cell nuclear antigen immunochemistry), and profibrotic gene expression (Collagen-α1, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase 1, and transforming growth factor beta 1) were assessed. The results indicated that the rats treated with NHF after PH had an increased liver size, a reduced amount of collagen, and a higher hepatocyte proliferation index compared with the rats that underwent PH alone. In addition, collagen-α1 gene expression was decreased in the NHF-treated rats. Thus, postoperative improvement in the liver morphology following NHF treatment may cause a significant decrease in the risk of liver failure and mortality after hepatic resection.
肝切除术是治疗某些肝脏疾病,特别是肝硬化患者肝癌的合适选择。然而,这种疾病会损害肝脏再生,从而增加肝衰竭和术后死亡的风险。对剩余肝脏再生的支持性治疗可能有助于这些患者的康复。我们证明,营养性肝营养因子(NHF)对接受部分肝切除术(PH)的大鼠肝硬化肝脏是一种有效的再生刺激。用硫代乙酰胺诱导肝硬化的大鼠接受PH,并分为2组。一组接受腹腔注射NHF,另一组接受盐溶液。12天后,评估生物统计学数据、胶原蛋白含量、肝细胞再生(增殖细胞核抗原免疫化学)和促纤维化基因表达(胶原蛋白-α1、基质金属蛋白酶2、金属蛋白酶组织抑制剂1和转化生长因子β1)。结果表明,与仅接受PH的大鼠相比,PH后接受NHF治疗的大鼠肝脏体积增大、胶原蛋白含量减少且肝细胞增殖指数更高。此外,NHF治疗的大鼠中胶原蛋白-α1基因表达降低。因此,NHF治疗后肝脏形态的术后改善可能会显著降低肝切除术后肝衰竭和死亡的风险。