Hyogo Hideyuki, Yamagishi Sho-ichi, Iwamoto Keiko, Arihiro Koji, Takeuchi Masayoshi, Sato Takashi, Ochi Hidenori, Nonaka Michihiro, Nabeshima Yoshitaka, Inoue Motoki, Ishitobi Tomokazu, Chayama Kazuaki, Tazuma Susumu
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
J Gastroenterol Hepatol. 2007 Jul;22(7):1112-9. doi: 10.1111/j.1440-1746.2007.04943.x. Epub 2007 Jun 7.
Advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate in diabetes, play important roles in the pathogenesis of diabetic vascular complications. Recently, AGE have also been found to be involved in insulin resistance. Although non-alcoholic steatohepatitis (NASH) is generally considered a hepatic manifestation of insulin resistance, there are no reports showing the link of AGE to NASH. The aim of this study was to evaluate the clinical significance of AGE in patients with NASH.
Glyceraldehyde-derived AGE levels were assayed from serum obtained from 106 patients: 66 with NASH, 10 with simple steatosis, and 30 controls.
Serum glyceraldehyde-derived AGE levels (U/mL) were significantly elevated in NASH patients (9.78 +/- 3.73) compared with simple steatosis (7.17 +/- 2.28, P = 0.018) or healthy controls (6.96 +/- 2.36, P = 0.003). Moreover, these were inversely correlated with adiponectin, an adipocytokine with insulin-sensitizing and anti-inflammatory properties. In addition, immunohistochemistry of glyceraldehyde-derived AGE showed intense staining in the livers of NASH patients.
The present data suggest that the sustained increase of glyceraldehyde-derived AGE could at least in part contribute to the pathogenesis of NASH. The serum glyceraldehyde-derived AGE level may be a useful biomarker for discriminating NASH from simple steatosis.
晚期糖基化终产物（AGE）是糖尿病中加速形成的衰老大蛋白衍生物，在糖尿病血管并发症的发病机制中起重要作用。最近，AGE也被发现与胰岛素抵抗有关。尽管非酒精性脂肪性肝炎（NASH）通常被认为是胰岛素抵抗的肝脏表现，但尚无报告显示AGE与NASH之间的联系。本研究的目的是评估AGE在NASH患者中的临床意义。
检测了106例患者血清中甘油醛衍生的AGE水平：66例NASH患者、10例单纯性脂肪变性患者和30例对照者。
与单纯性脂肪变性患者（7.17±2.28，P = 0.018）或健康对照者（6.96±2.36，P = 0.003）相比，NASH患者血清甘油醛衍生的AGE水平（U/mL）显著升高（9.78±3.73）。此外，这些水平与脂联素呈负相关，脂联素是一种具有胰岛素增敏和抗炎特性的脂肪细胞因子。另外，甘油醛衍生的AGE的免疫组化显示NASH患者肝脏中有强烈染色。
目前的数据表明，甘油醛衍生的AGE持续升高可能至少部分促成NASH的发病机制。血清甘油醛衍生的AGE水平可能是区分NASH与单纯性脂肪变性的有用生物标志物。
