Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat

Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat
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DOI:
10.1016/j.jhep.2004.02.005
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发表时间:
2004-06-01
影响因子:
25.7
通讯作者:
Wheatley, AM
Wheatley, AM
中科院分区:
医学1区
文献类型:
--
作者:
Mabuchi, A;Mullaney, I;Wheatley, AM

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背景/目的:已知肝星状细胞(HSC)在肝再生中发挥作用。我们研究了肝细胞/HSC相互作用和HSC激活后的不同时间在大鼠70%部分肝切除术(PHx)。方法:肝微循环研究,采用活体荧光显微镜(IVFM)。免疫组化法检测肝组织中结蛋白和α-SMA的表达。结果:IVFM显示,PHx后3天(PHx 3),肝实质细胞(PLC)和肝星状细胞(HSCs)中多见肝细胞团。HSC之间的距离从对照组的61.7 +/- 2.1 μ m下降到36.1 +/- 1.4 μ m(P < 0.001),而HSC/肝细胞比率上升(0.71 +/- 0.01到1.08 +/- 0.03; P < 0.001)。在PHx 3组中,在>80%的体内显微镜视野中,观察到HSC簇,特别是在肝细胞簇附近。在PHx 1和PHx 3,PLC级分中> 20%的细胞是粘附于肝细胞的HSC。在PHx 3,除了结蛋白染色,分离的HSC也对BrdU和α-SMA呈阳性,并形成簇。HSC中的HSC-馏分是阳性的结蛋白,这表明,粘附到肝细胞所需的HSC activation.Conclusions:我们的数据表明,HSC被激活粘附到肝细胞在肝再生的早期阶段。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版,保留所有权利。
Background/Aims: Hepatic stellate cells (HSCs) are known to play a role in hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC activation at various times after 70% partial hepatectomy (PHx) in the rat.Methods: The hepatic microcirculation was studied using intravital fluorescence microscopy (IVFM). Desmin and alpha-SMA within liver tissue were detected by immunohistochemistry. In isolated parenchymal liver cells (PLCs) and HSCs, double immunostaining was used to identify activated HSC.Results: Using IVFM, hepatocyte-clusters were often seen in vivo at 3 days after PHx (PHx3). Distance between HSC fell from 61.7 +/- 2.1 mum in controls to 36.1 +/- 1.4 mum (P < 0.001) while the HSC/hepatocyte ratio rose (0.71 +/- 0.01 to 1.08 +/- 0.03; P < 0.001). In >80% of in vivo microscopic fields in the PHx3 group, clusters of HSCs were observed especially near hepatocyte-clusters. At PHx1 and PHx3, > 20% of cells in the PLC-fraction were HSCs which adhered to hepatocytes. At PHx3, in addition to desmin staining, isolated HSCs were also positive for BrdU and alpha-SMA, and formed clusters. HSCs in the HSC-fraction were only positive for desmin which indicated that adherence to hepatocytes is required for HSC activation.Conclusions: Our data suggest that HSCs are activated by adhering to hepatocytes in the early phase of liver regeneration. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.