血管紧张素转换酶2基因转染对人内皮细胞MIF表达的影响

目的：探讨重组血管紧张素转换酶2（ACE2）基因转染对体外培养的人血管内皮细胞中由血管紧张素（Ang）II诱导的巨噬细胞移动抑制因子（MIF）表达的影响。方法:克隆和构建含人ACE2基因全长的重组质粒（pACE2），并将之转染入人血管内皮细胞中。分别采用实时定量PCR和Western印迹技术检测转染细胞中的MIF mRNA与蛋白表达情况。结果: Ang Ⅱ（100 nmol/L）和Ang IV（100 nmol/L）刺激后均可诱导人血管内皮细胞中MIF mRNA及蛋白表达增加（P<0.01）。pACE2基因转染可明显抑制内皮细胞中由Ang II和Ang IV诱导的MIF mRNA和蛋白表达（P<0.05）。结论: ACE2基因过表达可明显抑制人内皮细胞中炎症介质MIF的表达，提示ACE2基因具有一定的抗炎症效应。通过调节ACE2基因的活性和表达，很可能为炎症相关疾病如动脉粥样硬化治疗提供新的策略。

Effects of angiotensin-converting enzyme 2 gene transfection on the expression of macrophage migration inhibitory factor in human endothelial cells

AIM: To implore the effects of recombinant angiotensin- converting enzyme 2 (ACE2) gene transfection on the expression of macrophage migration inhibitory factor (MIF) induced by angiotensin (Ang) II in cultured human endothelial cells. METHODS: A recombinant plasmid encompassing human ACE2 gene (pACE2) was constructed and transfected into human endothelial cells. Endothelial cells were stimulated with Ang II or Ang IV in the presence and absence of pACE2 gene transfer. The mRNA and protein levels of MIF in endothelial cells were determined by real-time PCR and Western blotting, respectively. RESULTS: The mRNA and protein expressions of MIF were strikingly enhanced after exposures of endothelial cells to 100 nmol/L Ang Ⅱ and 100 nmol/L Ang Ⅳ (P<0.01, respectively). However, significant downregulations of MIF mRNA and protein expression were observed in endothelial cells pretreated with pACE2 gene transfer (P<0.05, respectively). CONCLUSION: ACE2 gene overexpression contributes to diminishments of inflammation mediator MIF expression in endothelial cells, suggesting that ACE2 gene has anti-inflammatory properties to some extent and may provide novel therapeutic strategies for the inflammation-related diseases such as atherosclerosis.