Mechanisms of aging and liver functions
Mechanisms of aging and liver functions
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DOI：
10.1159/000099475
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发表时间：
2007-01-01
影响因子：
2.3
通讯作者：
Annoni, Giorgio
中科院分区：
文献类型：
--
作者：
Gagliano, Nicoletta;Grizzi, Fabio;Annoni, Giorgio
背景/目的：形态功能研究表明，与其他器官相比，肝脏的老化程度相当好。它的成功归功于其持久的再生能力，即使细胞复制的潜力随着年龄的增长而逐渐下降。本研究的目的是分析肝再生早期阶段的某些方面、其产生应激反应的能力以及急性损伤早期的炎症反应。方法：2、6、12和19月龄大鼠单次腹腔注射CCl 4 ，2小时和24小时后进行形态学、生化和分子学评估。结果：从 12 个月大时开始，CCl4 后 AST 和 ALT 显着高于年轻大鼠。在 12 和 19 个月大的大鼠中，2 小时后即可检测到组织学改变，此后变得更加分散和明显，而在 2 和 6 个月大的大鼠中，仅在中毒 24 小时后才变得明显。从 12 月龄开始，CCl4 治疗 24 小时后，白蛋白、c-fos、c-myc、肝细胞生长因子、转化生长因子-α 和 HSP70 mRNA 水平下降。年轻大鼠的肥大细胞密度高于年老大鼠。结论：我们的结果表明：（a）老化肝脏的再生反应基本保留，尽管在某种程度上较弱且较慢，抵抗诱导细胞坏死的药物的能力降低； (b) HSP70 反应的减少表明体内平衡能力的降低，以及 (c) 衰老过程中炎症反应的降低。版权所有 (C) 2007 S. Karger AG，巴塞尔。
Background/Aims: Morphofunctional studies suggest that the liver, compared with other organs, ages fairly well. Its success is ascribable to its lasting ability to regenerate, even if the potential of the cells to replicate progressively declines with age. The aim of this study was to analyze some aspects of the early phases of liver regeneration, its capacity to mount a stress response, and the inflammatory response in the early stage of an acute injury. Methods: Rats aged 2, 6, 12 and 19 months received a single intraperitoneal injection of CCl 4, and morphological, biochemical and molecular evaluations were done 2 and 24 h later. Results: AST and ALT, starting at age 12 months, were significantly higher than in the younger rats after CCl4. Histological modifications were already detectable after 2 h in rats aged 12 and 19 months, thereafter becoming more diffuse and marked, whereas they become evident only 24 h after the intoxication in rats aged 2 and 6 months. Albumin, c- fos, c- myc, hepatocyte growth factor, transforming growth factor-alpha and HSP70 mRNA levels decreased 24 h after CCl4 starting at age 12 months. Mast cell density was higher in the young rats than the old ones. Conclusion: Our results point to: (a) a basically preserved regenerative response of the aged liver, although somehow weaker and slower, with reduced ability to counteract agents inducing cell necrosis; (b) a decrease in the HSP70 response suggesting a reduction in homeostatic capacity, and (c) a lower inflammatory response during aging. Copyright (C) 2007 S. Karger AG, Basel.