Division of Clinical Pharmacology , Indiana University, Indianapolis, IN 46202, USA.
Ann Surg. 2010 Jun;251(6):1041-8. doi: 10.1097/SLA.0b013e3181dbb572.
To evaluate the effects of surgical weight loss on hepatic lipid peroxidation levels and cytochrome P-450 protein expression in patients with nonalcoholic fatty liver disease (NAFLD).
NAFLD and nonalcoholic steatohepatitis (NASH) affect hepatic cytochrome P-450 (CYP) protein expression and activity, and CYP2E1 may play a role in the pathogenesis of NAFLD and NASH through induction of oxidative stress and lipid peroxidation. NAFLD and NASH are associated with increased systemic lipid peroxidation levels and elevated hepatic CYP2E1 activity, but hepatic CYP3A4/5 activity is decreased.
Liver biopsies from 20 patients with NAFLD who underwent bariatric surgery were obtained intraoperatively and at 15 +/- 7 months following surgery. Hepatic malondialdehyde (MDA) levels (a marker of lipid peroxidation), CYP2E1 and CYP3A4/5 protein expression, and steatosis, as a percent of total area, were measured by immunohistochemistry followed by digital image quantitation.
Following weight loss, as reflected by reduced BMI (54 +/- 9 vs. 37 +/- 9 kg/m2; P < 0.001), features of the metabolic syndrome, grade and stage of liver disease, and liver histology were all significantly improved (P < 0.01). Hepatic MDA staining (35 +/- 18% vs. 23 +/- 14%; P = 0.02), CYP2E1 protein content (68 +/- 9% vs. 56 +/- 11%; P < 0.001), and steatosis (17 +/- 7% vs. 2 +/- 3%; P < 0.001) were significantly reduced following weight loss. CYP3A4/5 protein content was unchanged (57 +/- 13% vs. 55 +/- 13%; P = 0.433). The reduction in lipid peroxidation was independently associated with changes in CYP2E1 protein expression after bariatric surgery (r = 0.477; P = 0.033).
Elevations in hepatic lipid peroxidation and CYP2E1 expression that are seen in NAFLD improve significantly with weight loss induced by bariatric surgery.
评估手术减肥对非酒精性脂肪性肝病（NAFLD）患者肝脂质过氧化水平和细胞色素 P-450 蛋白表达的影响。
NAFLD 和非酒精性脂肪性肝炎（NASH）影响肝细胞色素 P-450（CYP）蛋白表达和活性，CYP2E1 可能通过诱导氧化应激和脂质过氧化在 NAFLD 和 NASH 的发病机制中发挥作用。NAFLD 和 NASH 与全身性脂质过氧化水平升高和肝 CYP2E1 活性升高有关，但肝 CYP3A4/5 活性降低。
对 20 例接受减肥手术的 NAFLD 患者术中及术后 15±7 个月获得肝活检，通过免疫组织化学法和数字图像定量法检测肝丙二醛（MDA）水平（脂质过氧化的标志物）、CYP2E1 和 CYP3A4/5 蛋白表达以及作为总面积百分比的脂肪变性。
体重减轻反映为 BMI 降低（54±9 与 37±9kg/m2；P<0.001），代谢综合征特征、肝脏疾病分级和分期以及肝组织学均显著改善（P<0.01）。肝 MDA 染色（35±18%与 23±14%；P=0.02）、CYP2E1 蛋白含量（68±9%与 56±11%；P<0.001）和脂肪变性（17±7%与 2±3%；P<0.001）在体重减轻后显著降低。CYP3A4/5 蛋白含量无变化（57±13%与 55±13%；P=0.433）。减肥手术后，脂质过氧化的减少与 CYP2E1 蛋白表达的变化独立相关（r=0.477；P=0.033）。
NAFLD 中升高的肝脂质过氧化和 CYP2E1 表达在减肥手术后通过减肥手术引起的体重减轻显著改善。
