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Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver
Histochemistry and Cell Biology ( IF 2.1 ) Pub Date : 2021-09-15 , DOI: 10.1007/s00418-021-02030-8
Eddie Wisse 1 , Filip Braet 2 , Gerald J Shami 2 , Bartlomiej Zapotoczny 3 , Celien Vreuls 4 , Pauline Verhaegh 5 , Peter Frederik 6 , Peters J Peters 1 , Steven Olde Damink 7 , Ger Koek 5
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Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression.



中文翻译:

脂肪导致人脂肪肝实质细胞坏死和炎症

适应电子显微镜的固定方法使我们能够在 10 年的时间里研究 217 份完整人类肝脏的活组织检查中的肝细胞精细结构。出现了以下新的观察和概念:实质细胞中的单个脂肪滴可以生长到比原始细胞大四倍的体积,从而使所有细胞器的细胞质极度边缘化。单个实质细胞的坏死仍含有一个巨大的脂肪滴,表明在单细胞脂肪坏死过程中因脂肪而死亡。在单细胞脂肪坏死的后期,中性粒细胞和红细胞围绕单个脂肪滴,形成炎症性脂肪滤泡,表明炎症明显发作。此外,脂肪滴经常包含大量的丝状碎片和其他材料,最有可能代表马洛里物质。没有发现其他可能代表马洛里尸体的结构或材料。我们定期观察巨大脂肪滴的挤出,穿过实质细胞的外周细胞质、迪斯空间和内皮。这些脂肪滴以正弦脂质栓子的形式填充血窦。总之,适用于人体肝脏组织的固定方法表明,单个巨大的脂肪滴会导致单个实质细胞发生坏死和炎症。脂肪滴也会聚集 Mallory 物质并产生正弦脂肪栓子。因此,肝脏脱脂似乎是非酒精性脂肪肝疾病自我修复的必要治疗第一步。

更新日期:2021-09-16
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