Division of Gastroenterology/Hepatology, Indiana University, Indianapolis, IN 46202, USA.
J Clin Gastroenterol. 2011 Oct;45(9):800-7. doi: 10.1097/MCG.0b013e31821377e4.
To compare hepatic lipid peroxidation and cytochrome P-450 2E1 (CYP2E1) protein content in liver biopsies from children with nonalcoholic fatty liver disease (NAFLD) and 2 control groups.
Elevated hepatic lipid peroxidation resulting from increased hepatic CYP2E1 enzyme activity is involved in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) in adults, but studies in children are lacking.
Liver biopsies from 59 children with NAFLD (49 with NASH), 10 children with normal liver histology, and 9 children with mild chronic hepatitis C (HCV) infection were examined. Hepatic malondialdehyde (a measure of lipid peroxidation) levels and CYP2E1 protein content were quantitated, as a percentage of the 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 with biopsies from children with normal liver histology (7.6 ± 9.4%; P<0.001) or HCV infection (7.7 ± 7.6%; P<0.001). However, hepatic CYP2E1 expression was not different across the NAFLD, normal liver histology, and HCV groups (60.7 ± 8.7%, 53.5 ± 10.7%, and 60.0 ± 11.9%, respectively; P=0.116). Among children with NAFLD, lipid peroxidation and CYP2E1 protein content did not differ between biopsies with and without NASH. Body mass index was independently associated with hepatic lipid peroxidation levels (r=0.549; P<0.001).
Hepatic lipid peroxidation is increased in children with NAFLD but this is not related to hepatic CYP2E1 expression. No difference in lipid peroxidation in pediatric NAFLD versus NASH argues against a role in disease progression.
比较非酒精性脂肪性肝病（NAFLD）患儿与 2 个对照组肝活检组织中的肝脂质过氧化和细胞色素 P-450 2E1（CYP2E1）蛋白含量。
肝 CYP2E1 酶活性增加导致的肝脂质过氧化升高与成人非酒精性脂肪性肝炎（NASH）的发病机制有关，但在儿童中研究较少。
对 59 例非酒精性脂肪性肝病（NASH 患儿 49 例）、10 例正常肝组织学患儿和 9 例轻度慢性丙型肝炎（HCV）感染患儿的肝活检组织进行了检测。通过对肝活检组织进行免疫组化染色和数字图像定量，定量测定肝丙二醛（脂质过氧化的一种衡量指标）水平和 CYP2E1 蛋白含量占总面积的百分比。
与正常肝组织学活检（7.6 ± 9.4%；P<0.001）或 HCV 感染活检（7.7 ± 7.6%；P<0.001）相比，NAFLD 肝活检组织中的脂质过氧化明显增加（46.7 ± 20.8%）。然而，NAFLD、正常肝组织学和 HCV 组的肝 CYP2E1 表达无差异（分别为 60.7 ± 8.7%、53.5 ± 10.7%和 60.0 ± 11.9%；P=0.116）。在有或无 NASH 的 NAFLD 患儿中，肝活检组织的脂质过氧化和 CYP2E1 蛋白含量无差异。体重指数与肝脂质过氧化水平独立相关（r=0.549；P<0.001）。
NAFLD 患儿肝脂质过氧化增加，但与肝 CYP2E1 表达无关。儿科 NAFLD 与 NASH 之间的脂质过氧化无差异，表明其在疾病进展中不起作用。
