Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
J Clin Biochem Nutr. 2009 Nov;45(3):335-40. doi: 10.3164/jcbn.09-29. Epub 2009 Oct 28.
Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical hypoxemia through methemoglobinemia was induced by daily intraperitoneal injection of sodium nitrite (40 mg/kg) for 4 weeks in rats with fatty liver. The later was induced by 4-week feeding a choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups; Normal control, Hypoxemia, CDHF, and CDHF + hypoxemia. Nitrite was given for the later 4 weeks to each rat of Hypoxemia and CDHF + hypoxemia. CDHF + hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical liver dysfunction, while CDHF group was limited in mild steatosis, and Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent hypoxemia aggravate fatty liver to steatohepatitis and liver fibrosis.
最近的报告描述了阻塞性睡眠呼吸暂停患者中非酒精性脂肪性肝炎（NASH）的高发率。因此，我们假设复发性和间歇性低氧血症在 NASH 的发病机制中起重要作用。我们的目的是构建一个实用且准确的实验模型，以重现人类 NASH 的关键特征。通过每天向脂肪肝大鼠腹腔内注射亚硝酸钠（40mg/kg），诱导化学性低氧血症通过高铁血红蛋白血症，持续 4 周。脂肪肝通过 4 周喂养胆碱缺乏高脂饮食（CDHF）诱导。此外，用相同的方法制备正常饲料喂养组，但不进行 CDHF 喂养。动物实验分为四组：正常对照组、低氧血症组、CDHF 组和 CDHF+低氧血症组。低氧血症和 CDHF+低氧血症组的每只大鼠在后期 4 周给予亚硝酸盐。CDHF+低氧血症组大鼠出现类似于人类 NASH 患者的组织学变化，同时伴有生化肝功能障碍，而 CDHF 组仅局限于轻度脂肪变性，低氧血症组肝脏正常。本研究建立了一个可重现的有用的 NASH 模型，类似于人类 NASH 的主要特征，并首次表明复发性和间歇性低氧血症可加重脂肪肝向脂肪性肝炎和肝纤维化的发展。
