Downregulation of thrombomodulin contributes to ischemia‐reperfusion injury in mice with steatotic liver
Downregulation of thrombomodulin contributes to ischemia‐reperfusion injury in mice with steatotic liver
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血栓调节蛋白下调导致脂肪肝小鼠缺血再灌注损伤
DOI：
10.1111/hepr.13802
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发表时间：
2022
影响因子：
4.2
通讯作者：
Ohdan Hideki
中科院分区：
文献类型：
--
作者：
Yamaguchi Megumi;Tashiro Hirotaka;Kuroda Shintaro;Okimoto Sho;Kobayashi Tsuyoshi;Hinoi Takao;Ohdan Hideki
目的缺血再灌注（IR）损伤是肝脏手术（包括肝移植）最常见的并发症之一。脂肪变性肝脏特别容易受到IR损伤。然而，这种易感性增加的潜在机制尚未完全了解。在本研究中，我们使用异质血栓调节素（TM）敲除（KO） （TM+/−）小鼠，与野生型相比，表达约50%的TM功能活性，来研究TM失调是否会增强脂肪变性肝脏的IR损伤。方法采用胆碱缺乏饮食（CDD）诱导小鼠脂肪肝。利用蛋白c的生产力来评估TM的生物活性，比较脂肪变性肝脏和非脂肪变性肝脏对IR损伤的易感性，并在TM‐KO小鼠中进行评估。我们研究了重组TM （rTM）和TM的凝集素样结构域（rTM‐D1）是否能改善脂肪变性肝脏的IR损伤。结果与非脂肪变性小鼠相比，CDD喂养小鼠的蛋白C活性显著降低至20%以下。与非脂肪变性肝相比，脂肪变性肝表现出严重的IR损伤。重组TM （rTM）和TM的凝集素样结构域（rTM - D1）具有抗炎作用，可改善脂肪变性肝脏的IR损伤。TM+/−小鼠对IR损伤的易感性增加，rTM改善了inTM+/−小鼠的IR损伤。结论rTM的下调增加了脂肪变性肝脏对IR损伤的易感性，rTM通过抗炎作用改善了肝脏IR损伤。
AimIschemia‐reperfusion (IR) injury is one of the most critical complications commonly associated with liver surgery, including liver transplantation. Steatotic livers are particularly vulnerable to IR injury. However, the underlying mechanisms of this increased susceptibility have not fully been understood. In the present study, we used heterogeneous thrombomodulin (TM)‐knockout (KO) (TM+/−) mice, which express about 50% functional activity of TM as compared with wild type, to investigate whether dysregulation of TM enhances IR injury in steatotic livers.MethodsSteatotic livers were induced using choline‐deficient diets (CDD) in mice. The biological activity of TM was assessed using the productivity of protein C. Susceptibility to IR injury was compared between steatotic livers and non‐steatotic livers and also assessed in TM‐KO mice. We investigated whether recombinant TM (rTM) and the lectin‐like domain of TM (rTM‐D1) ameliorated IR injury in steatotic livers.ResultsProtein C activity was significantly decreased to less than 20% in CDD‐fed mice compared with mice with non‐steatotic livers. Steatotic livers showed exaggerated IR injury compared with non‐steatotic livers. Recombinant TM (rTM) and the lectin‐like domain of TM (rTM‐D1), which has anti‐inflammatory effects, ameliorated IR injury in steatotic livers.TM+/−mice showed increased susceptibility to IR injury, and rTM ameliorated the increased IR injury inTM+/−mice.ConclusionWe conclude that downregulation of TM increases susceptibility to hepatic IR injury in steatotic livers and that rTM ameliorates hepatic IR injury through anti‐inflammatory action.
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肝窦狭窄是缺乏胆碱饮食诱发大鼠脂肪性肝硬化门静脉高压的原因
DOI：
--
发表时间：
1974
期刊：
Acta pathologica japonica
影响因子：
--
作者：
Kazuyoshi Wada;K. Fujimoto;Yukimura Fujikawa;Y. Shibayama;Hideaki Mitsui;K. Nakata
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K. Nakata
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DOI：
10.1016/s1386-6346(01)00133-4
发表时间：
2002
期刊：
Hepatology research : the official journal of the Japan Society of Hepatology
影响因子：
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作者：
S. Miyamoto;S. Eguchi;N. Sugiyama;Y. Kawazoe;Y. Kamohara;H. Fujioka;K. Yanaga;J. Furui;T. Kanematsu
通讯作者：
T. Kanematsu
DOI：
10.1073/pnas.93.19.10212
发表时间：
1996-09-17
影响因子：
11.1
作者：
StearnsKurosawa, DJ;Kurosawa, S;Esmon, CT
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Esmon, CT
Rho抑制剂预防大鼠脂肪肝缺血再灌注损伤
DOI：
--
发表时间：
2012
期刊：
J Hepatology
影响因子：
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作者：
Kuroda S;Tashiro H;Igarashi Y;Tanimoto Y;Nambu J;Oshita A;Kobayashi T;Amano H;Tanaka Y;Ohdan H.
通讯作者：
Ohdan H.
影响因子：
8.8
作者：
Croome, Kristopher P.;Lee, David D.;Taner, C. Burcin
通讯作者：
Taner, C. Burcin