Impact of Age on Liver Regeneration Response to Injury After Partial Hepatectomy in a Rat Model

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• 作者：Juan Manuel S&aacute ; nchez-Hidalgo ; M.D. ; Ph.D.^&lowast ; ; &Aacute ; lvaro Naranjo ; M.D.^&lowast ; ; Rubé ; n Ciria ; M.D. ; Ph.D.^&lowast ; ; ^§ ; ; Isidora Ranchal ; Ph.D.^&dagger ; ; ^&Dagger ; ; ^§ ; ; Patricia Aguilar-Melero ; Ph.D.^&dagger ; ; ^§ ; ; Gustavo Ferrí ; n ; Ph.D.^&dagger ; ; ^&Dagger ; ; Amparo Valverde ; M.D.^&lowast ; ; ^§ ; ; Sebasti&aacute ; n Rufi&aacute ; n ; M.D. ; Ph.D.^&lowast ; ; ^§ ; ; Pedro Ló ; pez-Cillero ; M.D. ; Ph.D.^&lowast ; ; ^&Dagger ; ; ^§ ; ; Jordi Muntané ; Ph.D.^&dagger ; ; ^&Dagger ; ; ^§ ; ; Javier Briceñ ; o ; M.D. ; Ph.D.^&lowast ; ; ^&Dagger ; ; ^§ ; ; ^{javibriceno@hotmail.com}
• 关键词：aged ; liver resection ; proliferation ; oxidative stress ; TNF-伪 ; TGF-尾 ; IL-6 ; HGF ; nitric oxide ; regeneration
• 刊名：Journal of Surgical Research
• 出版年：2012
• 期刊代码：299_00224804
• 类别：med
• 出版时间：1 June, 2012
• 卷：175
• 期：1
• 页码：e1-e9
• 文件大小：1112 K

摘要

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Background

Liver resection is a feasible treatment for multiple liver diseases. There is no evidence about the impact of age on liver regeneration.

Objective

To assess the effect of age on liver regeneration in an experimental in聽vivo animal model of 70%-partial hepatectomy.

Methods

Forty young (Y) and old (O) Wistar male rats (n = 80) were distributed into four groups [controls (C), sham operated (SO), hepatectomy 6 h (H6), and 48 h (H48)]. Different morphometric and biochemical factors, oxidative and nitrosative stress, lipid peroxidation, cytokines kinetics, and histopathologic tissular parameters were determined.

Results

Early postoperative mortality was higher in aged rats (P = 0.049). Morphometric determinations, liver regeneration index, and total volume weight were favorable to young rats. Serum transaminase levels were higher in aged rats. Parameters of necrosis (measured by histopathologic injury [HI: 0-I-II-III]), regeneration (measured by bromodeoxyuridine-BrdU incorporation) and apoptosis (determined by the TDT-mediated dUTP nick end labeling-TUNEL) were well-synchronized in young rats. Parameters of oxidative stress such as reduced (GSH), oxidized (GSSG) glutathione and lipid peroxidation (measured by hepatic malondialdehyde -MDA-) were lower in young animals throughout the studied period. Nitrosative stress measured by nitric oxide (NO) end-products was higher in late stages in resected old rats. Pro-inflammatory cytokines (TNF- 伪) reached higher and earlier levels in aged rats while pro-regenerative cytokines (IL-6) were significantly higher in early stages for young rats and in late stages for aged rats. The levels of TGF-尾 were higher in young rats.

Conclusion

Liver regeneration is delayed and reduced in aged animals submitted to liver resection.