Augmentation of the early phase of liver regeneration after 70% partial hepatectomy in rats following selective Kupffer cell depletion
Augmentation of the early phase of liver regeneration after 70% partial hepatectomy in rats following selective Kupffer cell depletion
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DOI：
10.1016/s0168-8278(98)80013-5
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发表时间：
1998-08-01
影响因子：
25.7
通讯作者：
Hodgson, HJF
中科院分区：
文献类型：
--
作者：
Boulton, RA;Alison, MR;Hodgson, HJF
背景/目的：枯否细胞位于肝窦内，与肝细胞相邻，并产生一系列参与调节肝细胞增殖的生长调节分子。体外观察结果表明枯否细胞对肝细胞DNA合成具有刺激和抑制作用。我们旨在确定部分肝切除术后早期再生过程中枯否细胞活性的总体影响。方法：我们研究了部分肝切除术诱导的大鼠肝细胞DNA合成，然后通过脂质体包封的二氯亚甲基二膦酸盐（Cl 2 MBP）选择性消除枯否细胞。结果：我们证明了肝再生的早期阶段在枯否氏细胞耗竭后得到了增强，正如更大比例的肝细胞进行DNA合成所示，和较高的有丝分裂指数。这与肝脏中生长因子平衡的改变有关;肝细胞生长因子和转化生长因子β mRNA在枯否细胞耗竭的动物中减少，而IL-1 β mRNA不存在。此外，在没有部分肝切除术的情况下，选择性耗尽枯否细胞导致肝细胞在静息肝脏中增殖的增加进行DNA synthesization.Conclusion：耗尽肝脏枯否细胞的总体效果是提高肝细胞的增殖率，无论是部分肝切除术后，在静息状态。
Background/Aims: Kupffer cells are located in the liver sinusoids adjacent to hepatocytes and elaborate a range of growth regulatory molecules involved in regulating hepatocyte proliferation. In vitro observations imply the potential for Kupffer cells to exert both stimulatory and inhibitory influences on hepatocyte DNA synthesis. We aimed to determine the overall effect of Kupffer cell activity during the early regenerative processes after partial hepatectomy,Methods: We investigated hepatocyte DNA synthesis, induced by partial hepatectomy in rats, following selective elimination of Kupffer cells by liposome encapsulated dichlormethylene bisphosphonate (Cl2MBP),Results: We demonstrate that the early phase of liver regeneration was enhanced following Kupffer depletion, as indicated by a greater proportion of hepatocytes undergoing DNA synthesis, and a higher mitotic index. This was associated with an alteration in the balance of growth factors in the liver; HGF and TGF beta mRNA were reduced in Kupffer cell-depleted animals, and IL-1 beta mRNA was absent. In addition, in the absence of partial hepatectomy, the selective depletion of Kupffer cells leads to an increase in the proliferation of hepatocytes in resting liver undergoing DNA synthesis.Conclusion: The overall effect of depleting the liver of Kupffer cells is to enhance the proliferation rate of hepatocytes, both after partial hepatectomy and in the resting state.