Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats
Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats
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DOI：
10.1152/ajpgi.1996.270.6.g909
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发表时间：
1996-06-01
影响因子：
4.5
通讯作者：
Diehl, AM
中科院分区：
文献类型：
--
作者：
Rai, RM;Yang, SQ;Diehl, AM
尽管之前的研究表明肿瘤坏死因子-α (TNF) 可促进部分肝切除术 (PH) 后的肝脏再生，但 TNF 的来源尚不清楚。如果 Kupffer 细胞在 PH 后释放 TNF，则氯化钆 (GdCl) 消耗 Kupffer 细胞会抑制肝再生。为了验证这一假设，我们对 GdCl 处理组和对照组大鼠的细胞因子表达和再生事件进行了比较。库普弗细胞特异性 mRNA 的功能测定和 Northern 印迹分析证实，GdCl 耗尽了库普弗细胞。尽管如此，对总肝 RNA 的半定量逆转录聚合酶链反应分析显示，GdCl 处理的大鼠中 TNF 转录物水平高出六到八倍。在该组中，PH 导致白细胞介素 6（一种 TNF 诱导型细胞因子）的诱导增加 12 至 16 倍，以及多种细胞因子调节基因（c-jun、C/EBP-beta 和 C/EBP-delta）的诱导增加 2 至 3 倍。 GdCl 还放大了与再生相关的 AP-1（一种生长调节转录因子）的 DNA 结合活性的增加。此外，GdCl处理的大鼠中[H-3]胸苷的肝脏掺入、S期抗原的表达、增殖细胞核抗原和肝细胞有丝分裂指数均显着更高。因此，虽然 GdCl 会导致库普弗细胞耗竭，但它不会减少肝脏 TNF，实际上会增强 PH 后的肝脏再生。
Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release TNF after PH, then Kupffer cell depletion by gadolinium chloride (GdCl) should inhibit liver regeneration. To test this hypothesis, cytokine expression and regenerative events were compared in GdCl-treated and control rats. Functional assays and Northern blot analysis of a Kupffer cell-specific mRNA confirmed that GdCl depleted Kupffer cells. Despite this, semiquantitative reverse transcription-polymerase chain reaction analysis of total hepatic RNA showed six- to eightfold higher levels of TNF transcripts in GdCl-treated rats. In this group, PH caused 12- to 16-fold greater induction of interleukin-6, a TNF-inducible cytokine, and two- to threefold greater induction of several cytokine-regulated genes (c-jun, C/EBP-beta, and C/EBP-delta). GdCl also amplified regeneration-associated increases in the DNA binding activity of AP-1, a growth regulatory transcription factor. Furthermore, hepatic incorporation of [H-3]thymidine, expression of the S-phase antigen, proliferating cell nuclear antigen, and the hepatocyte mitotic index were each significantly greater in GdCl-treated rats. Thus, although GdCl causes Kupffer cell depletion, it does not decrease liver TNF and actually enhances liver regeneration after PH.