Inhibition of Toll-like Receptor 4 With Vasoactive Intestinal Peptide Attenuates Liver Ischemia-Reperfusion Injury
Inhibition of Toll-like Receptor 4 With Vasoactive Intestinal Peptide Attenuates Liver Ischemia-Reperfusion Injury
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DOI：
10.1016/j.transproceed.2011.01.191
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发表时间：
2011-06-01
影响因子：
0.9
通讯作者：
Xu, X.
中科院分区：
文献类型：
--
作者：
Jiang, W.;Tang, W.;Xu, X.
背景近年来，Toll样受体4（TLR 4）在缺血再灌注损伤中的作用受到了广泛关注。血管活性肠肽（VIP）在多种动物模型中发挥重要的抗炎和免疫调节作用。目前还没有关于VIP对IR损伤中TLR 4表达的影响的数据。本研究采用小鼠部分IR模型和小鼠巨噬细胞系RAW 264.7，观察VIP对TLR 4表达的影响。评估VIP对小鼠巨噬细胞系和部分热肝IR损伤小鼠模型中TLR 4 mRNA和蛋白的潜在抑制作用。我们还评估了肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6在该模型中的表达。VIP处理小鼠巨噬细胞系RAW 264.7后6、12和24 h TLR 4 mRNA表达水平显著降低。IR组TLR 4 mRNA、TLR 4蛋白、丙氨酸氨基转移酶、TNF-α和IL-6水平的表达显着增加，但5和10 nmol VIP预处理组的表达显着降低。苏木精-伊红染色显示，IR组大鼠脑组织水肿、坏死明显，VIP预处理组大鼠脑组织水肿、坏死明显减轻。本研究表明，VIP在体内外均能抑制TLR 4的活化，VIP预处理可抑制TLR 4的活化，减轻热IR损伤。
Background. Toll-like receptor 4 (TLR4) has attracted a great deal of attention in ischemia-reperfusion (IR) injury in recent years. Vasoactive intestinal peptide (VIP) plays an important role in anti-inflammatory and immunomodulatory activity in several animal models. There are no data available regarding the effect of VIP on TLR4 expression in IR injury in vivo. In the present study, we study the effect of VIP on TLR4 expression in mouse macrophage cell line RAW 264.7 and a mouse partial IR model.Methods. The potential inhibitory effect of VIP on TLR4 mRNA and protein in a mouse macrophage cell line and in a mouse model of partial warm hepatic IR injury was assessed. We also assessed the expression tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in this model.Results. Expression of TLR4 mRNA levels was significantly decreased at 6, 12, and 24 hours after treat with VIP in mouse macrophage cell line RAW 264.7. Expression of TLR4 mRNA, TLR4 protein, alanine aminotransferase, TNF-alpha, and IL-6 levels were significantly increased in the IR group but significantly decreased in groups pretreated with VIP at a concentration of 5 and 10 nmol. Hematoxylin and eosin staining show apparent edema and necrosis were observed in the IR group, but in the VIP pretreatment group, edema and necrosis in IR modes were reduced.Conclusion. This study showed that VIP might inhibit TLR4 in vitro and in vivo, and pretreatment with VIP might inhibited TLR4 activation and reduced warm IR injury.