Hepatic Ischemic Preconditioning Alleviates Ischemia-Reperfusion Injury by Decreasing TIM4 Expression.
Hepatic Ischemic Preconditioning Alleviates Ischemia-Reperfusion Injury by Decreasing TIM4 Expression.
复制标题
肝脏缺血预处理通过减少 TIM4 表达减轻缺血再灌注损伤
DOI：
10.7150/ijbs.24898
复制
发表时间：
2018
影响因子：
9.2
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Zhang Y;Shen Q;Liu Y;Chen H;Zheng X;Xie S;Ji H;Zheng S
肝脏缺血再灌注损伤（IRI）是肝脏手术后并发症的主要原因，而缺血预处理（IPC）已被证实对缺血再灌注损伤具有保护作用。TIM-4活化在巨噬细胞介导的肝脏IRI中起重要作用。本研究旨在确定IPC是否通过抑制TIM-4活化来保护肝脏IRI。本研究采用热肝缺血（90 min）再灌注6 h模型。小鼠在有或没有缺血预处理和TIM 4阻断抗体的情况下经受缺血再灌注损伤。Western blot检测TIM 4蛋白和线粒体凋亡相关蛋白的表达。检测各组大鼠血清丙氨酸转氨酶（ALT）、天门冬氨酸转氨酶（AST）水平，并进行肝细胞凋亡及病理学检查。结果发现，与对照组相比，缺血预处理可通过减少肝细胞凋亡、ALT、AST、CD 68和CD 3阳性细胞、组织髓过氧化物酶活性（MPO）和下调TIM-4表达来减轻IRI。阻断TIM 4可使肝组织中CD 68和CD 3阳性细胞减少。输注活化的单核细胞后，IPC的肝细胞凋亡率、ALT、AST、CD 68和CD 3阳性细胞数明显增加，而TIM-4敲除的单核细胞则无此作用。这些结果表明，IPC通过下调TIM-4来保护肝脏免受IRI，并且表明TIM-4将是最小化IRI的新的治疗靶点。
Ischemia-reperfusion injury (IRI) of the liver is a primary cause of post-liver-surgery complications and ischemic preconditioning (IPC) has been verified to protect against ischemia-reperfusion injury. TIM-4 activation plays an important role in macrophage mediated hepatic IRI. This study aimed to determine whether IPC protects against hepatic IRI through inhibiting TIM-4 activation. In this study, a model of warm liver ischemia (90 min) and reperfusion for 6 h was used. Mice were subjected to ischemia-reperfusion injury with or without ischemic preconditioning and TIM4 blocking antibody. Western blot was determined to detect the expression of TIM4 protein and mitochondrial apoptosis-related protein expression. Liver function was evaluated using the level of alanine transaminase (ALT) and aspartate transaminase (AST), cell apoptosis and pathological examination. We found that compared with the control group, ischemic preconditioning reduced IRI by decreasing hepatocyte apoptosis, ALT, AST, CD68 and CD3 positive cells, tissue myeloperoxidase activity(MPO), and downregulating TIM-4 expression. TIM4 blocking could reduce CD68 and CD3 positive cells in liver. Furthermore, activated monocytes transfusion significantly abolished the protect effect of IPC with increased hepatocyte apoptosis, ALT, AST, CD68 and CD3 positive cells while TIM-4 knockdown monocytes lost this effect. These results suggested that IPC protects against hepatic IRI by downregulating TIM-4 and indicated TIM-4 would be a novel therapeutic target to minimize IRI.
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DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
通讯作者：
Korthuis, Ronald J.
DOI：
10.1073/pnas.0910359107
发表时间：
2010-05-11
影响因子：
11.1
作者：
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通讯作者：
Kuchroo, Vijay K.
影响因子：
25.7
作者：
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通讯作者：
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影响因子：
37.8
作者：
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通讯作者：
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DOI：
10.1073/pnas.0910929107
发表时间：
2010-05-11
影响因子：
11.1
作者：
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通讯作者：
Ouyang, Wenjun