Gadolinium chloride suppresses acute rejection and induces tolerance following rat liver transplantation by inhibiting Kupffer-cell activation.

Gadolinium chloride suppresses acute rejection and induces tolerance following rat liver transplantation by inhibiting Kupffer-cell activation.
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氯化钆通过抑制枯否细胞活化来抑制大鼠肝移植后的急性排斥反应并诱导耐受

DOI:
10.3892/etm.2014.2015
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发表时间:
2014-12
影响因子:
2.7
通讯作者:
Zhang W
Zhang W
中科院分区:
医学4区
文献类型:
--
作者:
Wu Y;Wang Y;Li M;Yang X;Gong J;Zhang W

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本研究旨在探讨氯化钆(GdCl 3)抑制大鼠肝移植枯否细胞(KC)活化的机制及其抑制急性排斥反应和诱导耐受的能力。将大鼠随机分为对照组、GdCl 3预处理组和生理盐水预处理组。观察各组大鼠存活率、肝功能、肝脏病理组织学、肝胆汁细胞因子水平、KCs活化B细胞核因子κ轻链增强子(NF-κB)活性及KCs膜分子表达水平。GdCl 3组1个月生存率明显高于生理盐水组(P<0.05)。移植手术后,GdCl 3组的肝功能逐渐恢复;然而,生理盐水组的肝功能逐渐恶化。GdCl 3组肝脏病理组织学变化较小,而生理盐水组发生典型的急性排斥反应。GdCl 3组与对照组和生理盐水组相比,IFN γ和IL-2水平显著降低,IL-10水平显著升高(均P<0.01)。GdCl 3组和对照组的IL-4水平相似。生理盐水组NF-κB活性明显高于对照组和GdCl 3组(P<0.01)。GdCl 3组KC膜上主要组织相容性复合物-II、分化簇(CD)80和CD 86的表达水平明显低于对照组(P<0.05),而生理盐水组KC膜上这些蛋白的表达水平明显高于对照组(P<0.05)。提示GdCl_3能有效抑制KCs的免疫活性,抑制大鼠肝移植急性排斥反应,诱导移植耐受。
The aim of the present study was to investigate the mechanism by which gadolinium chloride (GdCl3) inhibits Kupffer cell (KC) activation and its ability to suppress acute rejection and induce tolerance following liver transplantation in rats. Rats were randomly divided into control, liver transplantation with GdCl3 pretreatment and liver transplantation with normal saline pretreatment groups. The survival rate, liver function, hepatic pathological histology, cytokine levels in the liver and bile, activity of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in KCs, and expression levels of membranous molecules on the KCs were observed. It was identified that the one-month survival rate in the GdCl3 group was significantly higher compared with that in the saline group (P<0.05). The liver function in the GdCl3 group gradually recovered following transplantation surgery; however, it progressively deteriorated in the saline group. There were minor changes of hepatic pathological histology in the GdCl3 group, whereas changes typical of acute rejection occurred in the saline group. In the GdCl3 group, the levels of interferon γ and interleukin (IL)-2 were significantly lower whereas the levels of IL-10 were significantly higher compared with those in the control and saline groups (all P<0.01). The IL-4 levels in the GdCl3 and control groups were similar. The activity of NF-κB in the saline group was significantly higher compared with those in the control and GdCl3 groups (P<0.01). The expression levels of major histocompatibility complex-II, cluster of differentiation (CD)80 and CD86 on the KC membranes in the GdCl3 group was significantly lower compared with those in the control group (P<0.05); however, these membranous proteins were highly expressed in the saline group. These data indicate that GdCl3 efficiently inhibits the immunological activity of KCs, suppresses acute rejection and induces tolerance following liver allograft transplantation in rats.
DOI: 10.1016/j.transproceed.2008.08.014
发表时间: 2008-10-01
影响因子: 0.9
作者:
Chen, Y.;Chen, J.;Gong, J.
通讯作者: Gong, J.
DOI: 10.1111/imm.12092
发表时间: 2013-08-01
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期刊: FASEB JOURNAL
影响因子: 4.8
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DOI: 10.1016/j.jss.2008.09.019
发表时间: 2010-03-01
影响因子: 2.2
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DOI: 10.1007/s004230050095
发表时间: 1998-03-01
影响因子: 2.3
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