Hepatic lipid peroxidation and cytochrome P-450 2E1 in pediatric nonalcoholic fatty liver disease and its subtypes.
Hepatic lipid peroxidation and cytochrome P-450 2E1 in pediatric nonalcoholic fatty liver disease and its subtypes.
复制标题
DOI：
10.1097/mcg.0b013e31821377e4
复制
发表时间：
2011-10
影响因子：
2.9
通讯作者：
Chalasani N
中科院分区：
文献类型：
--
作者：
Bell LN;Molleston JP;Morton MJ;Klipsch A;Saxena R;Vuppalanchi R;Chalasani N
由肝细胞色素P-450 2 E1（CYP 2 E1）酶活性增加引起的肝脏氧化应激和脂质过氧化水平升高被推测在非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）的发病机制中发挥作用。但对儿童的脂质过氧化和CYP 2 E1的研究还很缺乏。比较NAFLD儿童和两个对照组肝活检组织中的肝脏脂质过氧化和肝脏CYP 2 E1蛋白含量。对59例NAFLD儿童（49例NASH）、10例正常肝组织学儿童和9例慢性丙型肝炎感染（HCV）儿童的肝活检进行了检查。通过对肝活检材料进行免疫组织化学染色，然后进行数字图像定量，定量肝丙二醛（MDA，脂质过氧化的一种指标）水平和CYP 2 E1蛋白含量（占总面积的百分比）。NAFLD肝活检组织中的脂质过氧化（46.7 ± 20.8%）显著高于正常肝组织学（7.6 ± 9.4%; p<0.001）或HCV（7.7 ± 7.6%; p<0.001）儿童的肝活检组织。然而，与其他组相比，NAFLD活检中的肝脏CYP 2 E1并不高（p=）。在NAFLD儿童中，脂质过氧化和CYP 2 E1蛋白含量在有和没有NASH的活检组织中没有差异。BMI与肝脏脂质过氧化独立相关（r=0.549; p<0.001）。NAFLD儿童的肝脏脂质过氧化作用增加，但这与肝脏CYP 2 E1无关。不同NAFLD亚组之间脂质过氧化缺乏差异，这与其在疾病进展中的作用相矛盾。
Elevated hepatic oxidative stress and lipid peroxidation levels caused by increased hepatic Cytochrome P-450 2E1 (CYP2E1) enzyme activity has been speculated to play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). But studies of lipid peroxidation and CYP2E1 in children are lacking. To compare hepatic lipid peroxidation and hepatic CYP2E1 protein content in liver biopsies from children with NAFLD and two control groups. Liver biopsies from 59 children with NAFLD (49 with NASH), 10 children with normal liver histology, and 9 children with chronic hepatitis C infection (HCV) were examined. Hepatic malondialdehyde (MDA, a measure of lipid peroxidation) levels and CYP2E1 protein content were quantitated, as a percent of total area, by immunohistochemical staining of liver biopsy material followed by digital image quantitation. Lipid peroxidation was significantly greater in NAFLD liver biopsies (46.7 ± 20.8%) compared to liver biopsies from children with normal liver histology (7.6 ± 9.4%; p<0.001) or HCV (7.7 ± 7.6%; p<0.001). However, hepatic CYP2E1 was not higher in NAFLD biopsies compared to other groups (p=). Among children with NAFLD, lipid peroxidation and CYP2E1 protein content were not different between biopsies with and without NASH. The BMI was independently associated with hepatic lipid peroxidation (r=0.549; p<0.001). Hepatic lipid peroxidation is increased in children with NAFLD but this is not related to hepatic CYP2E1. Lack of difference in lipid peroxidation among different NAFLD subgroups argues against its role in the disease progression.