Hepatic 11beta-HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis
Hepatic 11beta-HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis
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DOI：
10.1111/j.1365-2265.2008.03358.x
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发表时间：
2009-04-01
影响因子：
3.2
通讯作者：
Quinkler, Marcus
中科院分区：
文献类型：
--
作者：
Konopelska, Sarah;Kienitz, Tina;Quinkler, Marcus
非酒精性脂肪肝是代谢综合征的肝脏表现。非酒精性脂肪性肝炎（NASH）是肝损伤的进展形式。导致NASH的病理生理机制尚不清楚，我们假设肝脏皮质醇代谢的改变可能是一个致病因素。75例患者（28名男性，47名女性）接受肝活检肝酶升高。组织学诊断确定8例正常肝脏，20例脂肪肝，22例NASH 1级，9例2级，3例3级，13例其他形式的肝炎或肝硬化。我们通过实时PCR定量肝脏11 β-羟基类固醇脱氢酶1型（11 β-HSD 1）和己糖-6-磷酸脱氢酶（H6 PDH）mRNA的表达。此外，使用GCMS分析24 h尿皮质醇代谢产物的排泄，并与健康对照组进行比较。与腰臀比呈负相关（R-2 = 0.809; P < 0.001）（R-2 = 0.394; P = 0.005），但与尿（THF + 5 α-THF）/THE比值、总皮质醇代谢产物排泄、年龄、BMI、脂肪肝程度或NASH分期无关。与健康对照组相比，脂肪肝或NASH患者的皮质醇代谢产物总排泄量增加。我们的数据表明，肝脏11 β-HSD 1和H6 PDH的表达密切相关。11 β-HSD 1基因表达似乎不参与脂肪肝或NASH的发病机制。然而，这些患者显示皮质醇的5 α和5 β减少增加，导致皮质醇周转率增加和HPA轴激活。
Nonalcoholic fatty liver disease represents the hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury. The pathophysiology that leads to NASH is not well understood.We hypothesize that an altered cortisol metabolism in the liver may be a pathogenetic factor.75 patients (28 men, 47 women) underwent liver biopsy for elevation in liver enzymes. Histological diagnosis identified normal liver in eight, fatty liver in 20, NASH grade 1 in 22, grade 2 in nine, grade 3 in three patients, and other forms of hepatitis or cirrhosis in 13 patients. We quantified hepatic 11 beta-hydroxysteroid dehydrogenase type1 (11 beta-HSD1) and hexose-6-phosphate-dehydrogenase (H6PDH) mRNA expression by real-time PCR. In addition, analysis of 24 h urinary excretion of cortisol metabolites using GCMS was performed and compared with healthy controls.11 beta-HSD1 mRNA expression correlated significantly (R-2 = 0.809; P < 0.001) with H6PDH mRNA expression, negatively with waist-to-hip ratio in women (R-2 = 0.394; P = 0.005), but not with urinary (THF + 5 alpha-THF)/THE ratio, total cortisol metabolite excretion, age, BMI, degree of fatty liver or NASH stages. Total cortisol metabolite excretion was increased in patients with fatty liver or NASH compared with healthy controls.Our data suggest that expression of hepatic 11 beta-HSD1 and H6PDH are closely interlinked. 11 beta-HSD1 gene expression does not seem to be involved in the pathogenesis of fatty liver or NASH. However, those patients showed an increased 5 alpha- and 5 beta-reduction of cortisol leading to an increased cortisol turnover rate and an activation of the HPA axis.