肝毒性化学物质和缺氧对肝脏非实质细胞的影响：用胶体碳灌注的大鼠肝脏Kupffer细胞的吞噬作用和内皮细胞的破坏☆
Effect of hepatotoxic chemicals and hypoxia on hepatic nonparenchymal cells: Impairment of phagocytosis by Kupffer cells and disruption of the endothelium in rat livers perfused with colloidal carbon☆
摘要
库普弗（Kupffer)细胞在肝脏功能和肝门静脉中外来颗粒的吞噬作用中起重要作用。因此，本研究的目的是研究几种肝毒性化学物质（烯丙醇，乙基己醇和甲萘醌）和缺氧对灌注大鼠肝脏中Kupffer细胞吞噬活性的影响。
最近开发的光学方法用于确定基于来自肝脏表面的反射光的变化，肝小叶的门静脉和周围区域中的库普弗细胞对碳颗粒的吞噬率（te Koppele，JM和Thurman，RG 1990.Am）。 J. Physiol.259，G814-G821）。研究了所有化学物质，从乳酸脱氢酶的释放评估，在实质细胞死亡之前，吞噬作用速度迅速下降（10-30分钟）。
这些化学物质破坏了实质细胞能量状态，如细胞死亡前抑制O2摄取和胆汁流动所示。当肝脏受损时，肝脏会膨胀，这一过程会增加灌注压力，理论上会破坏内皮并导致碳的非特异性摄取。
在具有肝毒性浓度的烯丙醇（350μm）的灌注中，在灌注70分钟后，碳颗粒积聚在肿胀的肝脏中。组织学研究表明，碳颗粒主要位于肝小叶的周围区域灌注中，并研究了所有肝毒性。当在没有肝毒性剂的情况下将灌注压升高至20cm H 2 O时，检测到的碳颗粒光学累积在肝小叶的上游区域（分别在顺行或逆行方向的灌注中的周围或周围区域）。
在非肿胀肝脏的扫描电子显微镜检查中，内皮保持完整。然而，在肿胀的肝脏中，内皮被破坏并且检测到碳非特异性地结合到实质细胞。加入烯丙醇后15分钟，胆小管扩张，内皮开窗扩大。在用烯丙醇灌注2小时后，肝脏超微结构被严重破坏。因此，可以得出结论，用肝毒性化学物质或缺氧灌注导致库普弗细胞的颗粒吞噬作用迅速减少，随后内皮细胞超微结构发生变化。
Effect of hepatotoxic chemicals and hypoxia on hepatic nonparenchymal cells: Impairment of phagocytosis by Kupffer cells and disruption of the endothelium in rat livers perfused with colloidal carbon☆
Abstract
Kupffer cells play an important role in liver function and phagocytosis of foreign particles in the hepatic portal tract. Therefore, the purpose of this study was to investigate the influence of several hepatotoxic chemicals (allyl alcohol, ethylhexanol, and menadione) and hypoxia on phagocytic activity of Kupffer cells in perfused rat liver.
A recently developed optical method was used to determine rates of phagocytosis of carbon particles by Kupffer cells in periportal and pericentral regions of the liver lobule based on changes in reflected light from the liver surface (te Koppele, J. M., and Thurman, R. G. 1990. Am. J. Physiol.259, G814–G821). With all chemicals studied, a rapid (10–30 min) decline in the rate of phagocytosis preceded parenchymal cell death as assessed from release of lactate dehydrogenase.
These chemicals impaired parenchymal cell energy status as indicated by inhibition of O2 uptake and bile flow prior to cell death. Livers swell when they are damaged, a process which increases perfusion pressure and could theoretically damage the endothelium and lead to nonspecific uptake of carbon.
In perfusions with a hepatotoxic concentration of allyl alcohol (350 μm), carbon particles accumulated in swollen livers after 70 min of perfusion. Histological studies revealed that carbon particles were localized predominantly in periportal regions of the liver lobule in perfusions with all hepatotoxicants studied. When perfusion pressure was elevated to 20 cm H2O in the absence of hepatotoxicants, carbon particles detected optically accumulated in upstream regions of the liver lobule (periportal or pericentral regions in perfusions in the anterograde or retrograde directions, respectively).
In scanning electron microscopy of nonswollen livers, the endothelium remained intact. In swollen livers, however, the endothelium was disrupted and carbon was detected bound nonspecifically to parenchymal cells. Fifteen minutes after addition of allyl alcohol, bile canaliculi were dilated and endothelial fenestrations were enlarged. After 2 hr of perfusion with allyl alcohol, hepatic ultrastructure was severely disrupted. Thus, it is concluded that perfusion with hepatotoxic chemicals or hypoxia results in a rapid decrease of particle phagocytosis by Kupffer cells followed by changes in endothelial cell ultrastructure.
Volume 110, Issue 1, August 1991, Pages 20-30
Toxicology and Applied Pharmacology
Author links open overlay panelJohan M.te Koppele∗2Barbara J.Keller∗Jane C.Caldwell-Kenkel†John J.Lemasters†Ronald G.Thurman∗
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https://doi.org/10.1016/0041-008X(91)90286-NGet rights and content
Effect of hepatotoxic chemicals and hypoxia on hepatic nonparenchymal cells: Impairment of phagocytosis by Kupffer cells and disruption of the endothelium in rat livers perfused with colloidal carbon - ScienceDirect https://www.sciencedirect.com/science/article/pii/0041008X9190286N
Review
The role of non-parenchymal cells in liver metabolism
Author links open overlay panelTheo J.C.van Berkel
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https://doi.org/10.1016/0968-0004(79)90080-XGet rights and content
Abstract
The biochemical characterization o f the different cell types found in the liver is now possible with the advent of methods for isolating and purifying parenchymal and non parenchymal cells. Biochemical and morphometric studies allow us to calculate the contributions that each type of cell makes to the functions of the liver. Nonparenchymal cells appear to specialize in the (specific) binding, uptake and degradation of materials from the blood circulation. It is also suggested that metabolic co-operation exists between the parenchymal and non-parenchymal cells.
The role of non-parenchymal cells in liver metabolism - ScienceDirect https://www.sciencedirect.com/science/article/pii/096800047990080X
