Dual Role of Vascular Endothelial Growth Factor in Hepatic Ischemia-Reperfusion Injury
Dual Role of Vascular Endothelial Growth Factor in Hepatic Ischemia-Reperfusion Injury
复制标题
DOI：
10.1097/01.tp.0000161627.84481.5e
复制
发表时间：
2005-05
期刊：
影响因子：
6.2
通讯作者：
Y. Tsurui;M. Sho;Y. Kuzumoto;K. Hamada;S. Akashi;H. Kashizuka;N. Ikeda;T. Nomi;T. Mizuno;H. Kanehiro;Y. Nakajima
中科院分区：
文献类型：
--
作者：
Y. Tsurui;M. Sho;Y. Kuzumoto;K. Hamada;S. Akashi;H. Kashizuka;N. Ikeda;T. Nomi;T. Mizuno;H. Kanehiro;Y. Nakajima
背景血管内皮生长因子（VEGF）是一种主要的血管生成因子，通过促进血管生成介导多种疾病。它还作为一种有效的促炎细胞因子在多种生理和病理免疫应答中发挥关键作用。在本研究中，我们评估了VEGF在肝脏热缺血再灌注（I/R）损伤中的表达，并在建立的小鼠模型中研究了重组人（rh）VEGF给药的效果。法采用70%部分肝缺血模型，采用实时定量聚合酶链反应和免疫组织化学方法检测I/R损伤时肝脏VEGF的表达。通过检测肝功能和组织学评价rhVEGF给药对I/R损伤的影响。此外，局部诱导型一氧化氮合酶（iNOS）和内皮NO合酶的表达进行了检查，以解决潜在的机制。结果缺血60 min再灌注2 h，VEGF表达明显上调。VEGF主要表达在浸润到缺血肝脏的CD 11b+细胞中。rhVEGF对肝脏缺血性损伤有明显的保护作用。这种作用与诱导型一氧化氮合酶表达上调有关。结论我们证明了VEGF在肝脏热I/R损伤中的双重作用。虽然内源性VEGF的表达和功能启动肝脏I/R损伤，外源性rhVEGF对缺血性肝脏有有益的作用。这些数据可能为VEGF的作用以及肝I/R损伤的病理生理学提供新的见解。
Background. Vascular endothelial growth factor (VEGF), a major angiogenic factor, mediates a variety of disease conditions through promotion of angiogenesis. It also plays a critical role as a potent proinflammatory cytokine in a variety of physiologic and pathologic immune responses. In the present study, we evaluated the expression of VEGF in hepatic warm ischemia-reperfusion (I/R) injury and examined the effect of recombinant human (rh)VEGF administration in an established murine model. Method. The expression of VEGF in the liver was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry during I/R injury using 70% partial hepatic ischemia model. The effect of rhVEGF administration on I/R injury was evaluated by measuring liver function and histology. In addition, local inducible nitric oxide synthase (iNOS) and endothelial NO synthase expressions were examined to address the underlying mechanisms. Results. The local expression of VEGF was significantly up-regulated at 2 hours after reperfusion after 60 minutes of ischemia compared with that in the naïve liver. VEGF was expressed predominantly in CD11b+ cells infiltrating into the ischemic liver. The administration of rhVEGF had a significant protective effect on ischemic injury in the liver. This effect was associated with the up-regulation of iNOS expression in the rhVEGF-treated liver. Conclusion. We demonstrate a dual role of VEGF in hepatic warm I/R injury. Although endogenous VEGF is expressed and functional to initiate hepatic I/R injury, exogenous rhVEGF has a beneficial effect on the ischemic liver. These data may provide new insights into the role of VEGF as well as pathophysiology of hepatic I/R injury.