Protective effect of heme oxygenase-1 on hepatic isch emia-reperfusion injury through inh ibition of platelet adhesion to the sinusoids
Protective effect of heme oxygenase-1 on hepatic isch emia-reperfusion injury through inh ibition of platelet adhesion to the sinusoids
复制标题
血红素加氧酶1通过抑制血小板与血窦黏附对肝缺血再灌注损伤的保护作用
DOI：
10.1016/j.jss.2012.11.030
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发表时间：
2013
期刊：
影响因子：
2.2
通讯作者：
Ohkohchi N
中科院分区：
文献类型：
--
作者：
Tamura T;Kondo T;Ogawa K;Fukunag a K;Ohkohchi N
血小板含有多种生长因子，包括血管内皮生长因子（VEGF）和胰岛素样生长因子。材料与方法：将严重联合免疫缺陷小鼠分别行70%肝切除术和磷酸盐缓冲盐水（PBS）; 70%肝切除术和人血小板输注（hPLT）; 70%肝切除术，KC耗竭和PBS（KD + PBS）; 70%肝切除术、KC耗竭和人血小板输注（KD + hPLT）;或假手术和人血小板输注（假手术）。评价各组的肝再生、人血小板在肝中的积累和活化、和/或血小板和KCs的共定位。与PBS、KD + PBS和KD + hPLT组相比，hPLT组在输血后48小时的肝体重比显著更高。hPLT组肝组织中人VEGF浓度较高，而其他组中未检测到VEGF。与PBS组相比，hPLT组中KC衍生的细胞因子的肝脏水平升高。这些细胞因子下游的信号级联中的分子在hPLT组中比在PBS组中更早且更稳健地磷酸化。在hPLT组中，活化的人血小板在肝脏中积累，而在假手术组和KD + hPLT组中，血小板积累较少，并且许多血小板未活化。在hPLT组，大多数人血小板附着KCs. CONCLUSIONSHAN血小板输注促进严重联合免疫缺陷小鼠肝再生。人血小板和KCs一起导致生长因子释放和增强肝再生。
BACKGROUNDPlatelets contain several growth factors, including vascular endothelial growth factor (VEGF) and insulin-like growth factor. We examined the role of human platelets in liver regeneration with a focus on Kupffer cells (KCs).MATERIALS AND METHODSSevere combined immunodeficiency mice were subjected to 70% hepatectomy and phosphate-buffered saline administration (PBS); 70% hepatectomy and human platelet transfusion (hPLT); 70% hepatectomy, KC depletion, and PBS administration (KD + PBS); 70% hepatectomy, KC depletion, and human platelet transfusion (KD + hPLT); or a sham operation and human platelet transfusion (sham). The groups were evaluated for liver regeneration, accumulation and activation of human platelets in the liver, and/or co-localization of platelets and KCs.RESULTSThe liver-to-body weight ratio was significantly higher 48 h post-transfusion in the hPLT group compared with the PBS, KD + PBS, and KD + hPLT groups. Human VEGF concentrations were higher in liver tissues from the hPLT group, whereas VEGF was not detected in the other groups. Hepatic levels of KC-derived cytokines were elevated in the hPLT group compared with the PBS group. Molecules in signaling cascades downstream of these cytokines were phosphorylated earlier and more robustly in the hPLT group than in the PBS group. Activated human platelets accumulated in livers in the hPLT group, whereas fewer platelets accumulated and many were not activated in the sham and KD + hPLT groups. In the hPLT group, most human platelets were attached to KCs.CONCLUSIONSHuman platelet transfusion promoted liver regeneration in severe combined immunodeficiency mice. Together, human platelets and KCs resulted in growth factor release and enhanced liver regeneration.