CD14 expression and Kupffer cell dysfunction in non-alcoholic steatohepatitis: Superparamagnetic iron oxide-magnetic resonance image and pathologic correlation

CD14 expression and Kupffer cell dysfunction in non-alcoholic steatohepatitis: Superparamagnetic iron oxide-magnetic resonance image and pathologic correlation
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DOI:
10.1111/j.1440-1746.2011.07057.x
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发表时间:
2012-04-01
影响因子:
4.1
通讯作者:
Ueno, Takato
Ueno, Takato
中科院分区:
医学3区
文献类型:
--
作者:
Tonan, Tatsuyuki;Fujimoto, Kiminori;Ueno, Takato

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背景与目的:枯否细胞(Kupffer cell,KC)功能和CD14表达参与了非酒精性脂肪性肝炎(NASH)的发病过程。然而,这些关系仍然不清楚。我们探讨了超顺磁性氧化铁增强磁共振成像(SPIO-MRI)与NASH的组织病理学严重程度以及NASH中CD14阳性的KC数目之间的关系。方法:32例NASH患者,其中24例为NASH患者,8例为单纯性脂肪变性患者,行SPIO-MRI T2加权梯度回声序列检查。所有受试者均经病理诊断,并进行坏死性炎症分级、纤维化分期和CD14阳性KC数量的评估。对NASH和单纯性脂肪变性的患者进行比较,采用Mann Whitney检验确定作为KC功能替代参数的肝脏与肌肉信号强度比(Reduction-%LMR)和CD14阳性KC数量的差异。用Kruskal Wallis检验和Pearson相关系数分析LMR减少率与组织病理学严重程度和CD14阳性KC数之间的关系。结果:NASH组和单纯性脂肪变性组LMR减少率和CD14阳性KC数有统计学意义(Mann Whitney检验,P<0.001)。减少%LMR随坏死性炎症分级或纤维化分期的增加而降低。随着炎症分级和纤维化分期的增加,CD14阳性的KC数量增加(Kruskal Wallis检验,两者,P<0.001)。CD14阳性KC数与LMR减少率高度相关(Pearson r=0.81;P<0.001)。结论:SPIO-MRI评价KC吞噬功能与组织学严重程度及CD14阳性KC数有关。这些结果支持KC吞噬功能障碍在NASH发病机制中的作用。
Background and Aim: Kupffer cell (KC) function and CD14 expression contributes to pathogenesis of non-alcoholic steatohepatitis (NASH). However, these relationships remain unclear. We investigated the relationship of KC function with superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), histopathological severity of NASH, and number of CD14-positive KCs in NASH.Methods: This retrospective study included 32 patients (24 with NASH and eight with simple steatosis) who had previously undergone SPIO-MRI with T2-weighted gradient-recalled echo sequence. All subjects were diagnosed pathologically and were evaluated for necroinflammation grade, fibrosis stage, and number of CD14-positive KCs. Patients with NASH and simple steatosis were compared by using the Mann Whitney test to determine differences in percent reduction of liver-to-muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of KC function, and number of CD14-positive KCs. Kruskal Wallis test and Pearson's correlation coefficient were used to analyze relation among reduction-%LMR, histopathological severity and number of CD14-positive KCs.Results: There were statistically significant differences in reduction-%LMR and number of CD14-positive KCs between NASH and simple steatosis patients (Mann Whitney test, P < 0.001 for all comparisons). Reduction-%LMR decreased with an increase in necroinflammation grade or fibrosis stage. The number of CD14-positive KCs increased with an increase in necroinflammation grade and fibrosis stage (Kruskal Wallis test, both, P < 0.001). A high correlation was seen between number of CD14-positive KCs and reduction-%LMR (Pearson r = 0.81; P < 0.001Conclusions: KC phagocytic function evaluated with SPIO-MRI correlated with histopathological severity and number of CD14-positive KCs. These results support the concept that KC phagocytic dysfunction contributes to the pathogenesis of NASH.