Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease.
Hepatic reticuloendothelial system cell iron deposition is associated with increased apoptosis in nonalcoholic fatty liver disease.
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DOI：
10.1002/hep.26238
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发表时间：
2013-05
期刊：
影响因子：
13.5
通讯作者：
Kowdley, Kris V.
中科院分区：
文献类型：
--
作者：
Maliken, Bryan D.;Nelson, James E.;Klintworth, Heather M.;Beauchamp, Mary;Yeh, Matthew M.;Kowdley, Kris V.
本研究的目的是探讨非酒精性脂肪性肝病中肝脏铁沉积、细胞凋亡、组织学特征以及氧化应激和细胞死亡的血清标志物之间的关系。对来自单一中心的 83 名未经选择的经活检证实的非酒精性脂肪性肝病 (NAFLD) 患者进行了临床、生化、代谢和独立组织病理学评估。使用血清细胞角蛋白-18 (CK18) M30 和 M65 ELISA 对血清中的细胞凋亡和坏死进行定量，并通过原位 TUNEL 染色对肝脏中的细胞凋亡和坏死进行定量。测量血清丙二醛（MDA）和硫氧还蛋白-1（Trx-1）水平以评估氧化应激。肝脏中网状内皮系统细胞 (RES) 铁的存在与非酒精性脂肪性肝炎 (p<0.05) 和肝脏 TUNEL 染色增加 (p=0.02) 以及凋亡特异性 (M30, p=0.013) 和总 (M65, p=0.006) CK-18 片段的血清水平增加、较高的 MDA (p=0.002) 和与没有可染色肝铁的患者相比，抗氧化剂 Trx-1 水平较低 (p=0.012)。与没有可染色肝铁的受试者相比，具有肝细胞铁染色模式的 NAFLD 患者血清 MDA 水平也有所升高 (p=0.006)，但 M30 CK-18 水平或 TUNEL 染色没有升高。铁沉积仅限于肝细胞的患者的凋亡特异性 M30 片段相对于总 M65 CK-18 水平较低（37% vs. ≤ 25%，p<0.05）。肝 RES 细胞中铁的存在与 NASH、细胞凋亡增加和氧化应激增加有关。 NAFLD 中的肝细胞铁沉积也与氧化应激有关，并可能促进该疾病中的肝细胞坏死。
The goal of this study was to examine the relationship between presence of hepatic iron deposition, apoptosis, histologic features and serum markers of oxidative stress and cell death in nonalcoholic fatty liver disease. Clinical, biochemical, metabolic and independent histopathologic assessment was conducted in 83 unselected patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD)from a single center. Apoptosis and necrosis in serum was quantified using serum cytokeratin-18(CK18) M30 and M65ELISAsand in liver by TUNEL stainingin situ. Serum malondialdehyde(MDA) and thioredoxin-1 (Trx-1) levels were measured to evaluate oxidative stress. Presence of reticuloendothelial system cell (RES) iron in the liver was associated with nonalcoholic steatohepatitis (p<0.05) and increased hepatic TUNEL staining (p=0.02),as well as increased serum levels of apoptosis-specific (M30, p=0.013) and total (M65, p=0.006) CK-18 fragments, higher MDA (p=0.002) and lower antioxidant Trx-1 levels (p=0.012) compared to patients without stainable hepatic iron. NAFLD patients with a hepatocellular iron staining pattern also had increased serum MDA (p=0.006) but not M30 CK-18 levels or TUNEL staining compared to subjects without stainable hepatic iron. Patients with iron deposition limited to hepatocytes had a lower proportion of apoptosis-specific M30 fragments relative to total M65 CK-18 levels (37% vs. ≤ 25%, p<0.05). Presence of iron in liver RES cells is associated with NASH, increased apoptosis and increased oxidative stress. Hepatocellular iron deposition in NAFLD is also associated with oxidative stress and may promote hepatocyte necrosis in this disease.
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影响因子：
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