Higher Activity of Alcohol Dehydrogenase Is Correlated with Hepatic Fibrogenesis
Higher Activity of Alcohol Dehydrogenase Is Correlated with Hepatic Fibrogenesis
复制标题
乙醇脱氢酶的较高活性与肝纤维化相关
DOI：
10.1124/jpet.118.249425
复制
发表时间：
2018-12-01
影响因子：
3.5
通讯作者：
Qiao, Hai-Ling
中科院分区：
文献类型：
--
作者：
Gao, Na;Li, Jing;Qiao, Hai-Ling
肝纤维化可以进展为肝硬化和肝细胞癌（HCC）。预防、稳定和逆转疾病进展对肝纤维化患者至关重要，迫切需要确定肝纤维化的危险因素。在这项研究中，我们检测了乙醇脱氢酶（ADH）和乙醛脱氢酶（ALDH）的活性在肝细胞癌患者（n = 88）的肝纤维化，并与这些结果进行了比较，与正常肝脏患者（n = 74）的活动。本实验采用大鼠肝纤维化-肝癌模型，研究了ADH在肝纤维化和肝癌中的活性变化，以及ADH活性与肝纤维化和肝癌程度的关系。ADH和ALDH活性在正常肝脏中存在显著的个体间差异。纤维化肝组织中总ADH、ADHI和ADHII活性均显著高于正常肝组织（P < 0.001），而ALDH活性略高于正常肝组织（P < 0.001）。ADHI和ADHII的阳性率分别为84.1%和77.3%，受试者工作特征（ROC）曲线下面积分别为0.943和0.912。与对照组相比，模型组大鼠肝脏ADH活性在肝纤维化和肝细胞癌阶段均显著升高，而在这两个阶段肝脏ADH活性之间无显著差异。在肝纤维化阶段，血清ADH活性与肝纤维化程度（Masson面积%、Ki 67 +%、增殖细胞核抗原+%、GST-β平均密度）相关，而与肝细胞癌阶段无关。ADH活性升高是肝纤维化发生的危险因素，可能是肝纤维化的预防靶点。
Hepatofibrosis can progress to cirrhosis and hepatocellular carcinoma (HCC). Prevention, stabilization, and reversal of disease progression are vital for patients with hepatofibrosis, and identifying the risk factors for hepatofibrosis is urgently needed. In this study, we examined the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the fibrotic livers of HCC patients (n = 88) and comparied these results with activities in patients with normal livers (n = 74). A fibrosis-carcinoma rat model was used to study the activity of ADH in fibrosis and HCC and the relationship between innate ADH activity and the extent of hepatofibrosis or HCC. Substantial interindividual variations were found in the activities of ADH and ALDH in normal livers. The activity levels of total ADH, ADHI, and ADHII in fibrotic livers were significantly higher than those in normal livers (P < 0.001), whereas the activity of ALDH was slightly greater. The positive rates of ADHI and ADHII were 84.1% and 77.3%, respectively; the areas under the receiver operator characteristics (ROC) curve were 0.943 and 0.912, respectively. For the rat model compared with controls, ADH activity in liver was significantly increased at the fibrotic and HCC stages, and no significant difference was noted between ADH activity in the liver at these two stages. The innate activity of ADH in serum was well correlated with the extent of hepatofibrosis as indicated by Masson area%, Ki67+%, proliferating cell nuclear antigen +%, and GST-p average density at fibrotic stage but not at HCC stage. A higher level of activity of ADH is a risk factor for hepatofibrogenesis and might be a prevention target for hepatofibrosis.