Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression
Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression
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DOI：
10.1002/hep.21070
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发表时间：
2006-03-01
期刊：
影响因子：
13.5
通讯作者：
Ueda, M
中科院分区：
文献类型：
--
作者：
Ikura, Y;Ohsawa, M;Ueda, M
非酒精性脂肪性肝炎/非酒精性脂肪性肝病被认为是各种代谢紊乱的肝脏表现。然而，其确切的致病机制尚不清楚。氧化应激和随之而来的脂质过氧化似乎在疾病进展中起着关键作用。在这项研究中，我们分析了氧化磷脂酰胆碱（oxPC），脂质过氧化物，作为清道夫受体的配体，在这种脂肪变性疾病的患者的肝脏定位。非酒精性脂肪性肝病标本（15例尸检肝脏单纯脂肪变性和32例活检肝脏脂肪性肝炎）进行了检查，通过免疫组化和免疫电镜使用特异性抗体对oxPC。此外，还评估了病变肝脏中清道夫受体表达、肝细胞凋亡、铁沉积和炎性细胞浸润。氧化磷脂酰胆碱主要定位于脂肪变性肝细胞和一些巨噬细胞/枯否细胞。少数变性或凋亡肝细胞也呈oxPC阳性。免疫电镜显示oxPC定位于细胞质/胞质膜内，包括脂滴。脂肪肝表现为清道夫受体表达增强。oxPC细胞的数量与疾病的严重程度和髓过氧化物酶阳性中性粒细胞的数量相关，但与铁沉积的程度无关。总之，oxPC在肝组织中的独特定位表明，中性粒细胞髓过氧化物酶衍生的氧化应激可能是至关重要的oxPC的形成和脂肪性肝病的进展。
Nonalcoholic steatohepatitis/nonalcoholic fatty liver disease is considered to be a hepatic manifestation of various metabolic disorders. However, its precise pathogenic mechanism is obscure. Oxidative stress and consequent lipid peroxidation seem to play a pivotal role in disease progression. In this study, we analyzed the localization of oxidized phosphatidylcholine (oxPC), a lipid peroxide that serves as a ligand for scavenger receptors, in livers of patients with this steatotic disorder. Specimens of nonalcoholic fatty liver disease (15 autopsy livers with simple steatosis and 32 biopsy livers with steatohepatitis) were examined via immunohistochemistry and immunoelectron microscopy using a specific antibody against oxPC. In addition, scavenger receptor expression, hepatocyte apoptosis, iron deposition, and inflammatory cell infiltration in the diseased livers were also assessed. Oxidized phosphatidylcholine was mainly localized to steatotic hepatocytes and some macrophages/Kupffer cells. A few degenerative or apoptotic hepatocytes were also positive for oxPC. Immunoelectron microscopy showed oxPC localized to cytoplasmic/intracytoplasmic membranes including lipid droplets. Steatotic livers showed enhanced expression of scavenger receptors. The number of oxPC cells was correlated with disease severity and the number of myeloperoxidase-positive neutrophils, but not with the degree of iron deposition. In conclusion, distinct localization of oxPC in liver tissues suggest that neutrophil myeloperoxidase-derived oxidative stress may be crucial in the formation of oxPC and the progression of steatotic liver disease.