Effects of gadolinium chloride (GdCl3) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions
Effects of gadolinium chloride (GdCl3) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions
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DOI：
10.1016/j.jcpa.2005.01.011
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发表时间：
2005-08-01
影响因子：
0.8
通讯作者：
Yamate, J
中科院分区：
文献类型：
--
作者：
Ide, M;Kuwamura, M;Yamate, J
浸润受损组织的巨噬细胞在纤维发生中发挥重要作用。为了阐明巨噬细胞的功能作用，我们研究了硫代乙酰胺 (TAA) 诱导的大鼠肝脏损伤中巨噬细胞群的出现，无论是否经过 GdCl3（一种能够抑制库普弗细胞功能的化学物质）预处理。 GdCl3+TAA组大鼠单次腹腔注射GdCl3(7.5mg/kg体重)，24小时后单次静脉注射TAA(300mg/kg体重)。 TAA 组中的大鼠仅接受 TAA。两组大鼠在TAA注射后（PTI）第3、5和7天进行检查。在TAA组中，在PTI第3天，当TAA诱导的肝细胞损伤特别明显时，巨噬细胞数量达到峰值，随后下降，直到PTI第7天。与TAA组相比，GdCl3 + TAA组显示ED1免疫标记细胞数量显着减少 （渗出巨噬细胞）和 ED2 免疫标记细胞（库普弗细胞）在 PTI 第 3、5 和 7 天，以及 OX6 免疫标记细胞（抗原呈递巨噬细胞）在 PTI 第 3 和 5 天。虽然不那么引人注目，但 GdCl3 + 中α-平滑肌肌动蛋白阳性肌成纤维细胞和纤维化区域的数量减少 TAA组.通过RT-PCR，GdCl3+TAA组的PTI第3天和第7天TGF-β1 mRNA的表达受到抑制，并且通过用1％GdCl3处理大鼠巨噬细胞样细胞(HS-P)在体外证实了表达抑制。研究表明，GdCl3 治疗减少了肝脏病变中出现的巨噬细胞数量，并抑制了巨噬细胞中 TGF-β1 mRNA 的表达。巨噬细胞数量的减少可能有助于改善肝纤维化。 (c) 2005 Elsevier Ltd. 保留所有权利。
Macrophages infiltrating injured tissue play an important part in fibrogenesis. To shed light on the functional roles of macrophages, we investigated the appearance of macrophage populations in thioacetamide (TAA)-induced rat hepatic lesions, with or without pretreatment with GdCl3, a chemical capable of inhibiting Kupffer cell functions. In the GdCl3+TAA group rats received a single intraperitoneal injection of GdCl3, (7.5mg/kg body weight) and, after 24h, a single intravenous injection of TAA (300 mg/kg body weight). Rats in the TAA group received TAA only. Rats in both groups were examined on post-TAA injection (PTI) days 3, 5, and 7. In the TAA group, on PTI day 3, when TAA-induced hepatocyte injury was particularly prominent, the number of macrophages peaked, subsequently decreasing until PTI day 7. As compared with the TAA group, the GdCl3 + TAA group showed significantly decreased numbers of ED1-immunolabelled cells (exudate macrophages) and ED2-immunolabelled cells (Kupffer cells) on PTI days 3, 5, and 7, and OX6-immunolabelled cells (antigen-presenting macrophages) on PTI days 3 and 5. Although less strikingly, the numbers of alpha-smooth muscle actin-positive myofibroblasts and fibrotic areas were decreased in the GdCl3 + TAA group. By RT-PCR, the expression of TGF-beta 1 mRNA was suppressed on PTI days 3 and 7 in the GdCl3+TAA group, and the suppressed expression was confirmed in vitro by treating rat macrophage-like cells (HS-P) with 1% GdCl3. The study showed that GdCl3 treatment decreased the numbers of macrophages appearing in hepatic lesions and inhibited TGF-beta 1 mRNA expression in macrophages. Decreased numbers of macrophages may contribute to improvement of hepatic fibrosis. (c) 2005 Elsevier Ltd. All rights reserved.