Center for Vascular Biology Research, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA.
Shock. 2012 Apr;37(4):392-8. doi: 10.1097/SHK.0b013e318248225e.
Experimental sepsis was induced in male C57BL/6j, adiponectin-deficient mice (ADPNKO), and wild-type littermates by i.p. injection of 16 mg/kg lipopolysaccharide or cecal ligation and puncture. Blood and tissue samples were harvested 24 h after model induction. Circulating adiponectin is reduced in mice with endotoxemic challenge and after cecal ligation and puncture compared with healthy control mice. Quantitative reverse transcriptase-polymerase chain reaction for adiponectin reveals a pattern of response that is both model- and organ-specific. When challenged with sepsis, adiponectin deficiency results in increased expression of endothelial adhesion and coagulation molecules in the lung, liver, and kidney as quantified by reverse transcriptase-polymerase chain reaction, increased macrophage and neutrophil infiltration by immunohistochemistry, and vascular leakage in the liver and kidney. Adiponectin-deficient mice have reduced survival following cecal ligation and puncture and increased blood levels of interleukin 6, soluble vascular endothelial growth factor receptor 1, and soluble endothelial adhesion molecules E-selectin and intercellular adhesion molecule 1. Finally, ADPNKO promoted end-organ injury in the liver and kidney, whereas the lungs were not affected. These data suggest a protective role of adiponectin in diminishing microvascular organ-specific endothelial cell activation during sepsis.
实验性脓毒症通过腹腔内注射 16mg/kg 脂多糖或盲肠结扎和穿孔，在雄性 C57BL/6j、脂联素缺乏小鼠（ADPNKO）和野生型同窝仔鼠中诱导。模型诱导后 24 小时采集循环血液和组织样本。与健康对照小鼠相比，内毒素攻击和盲肠结扎和穿孔后的循环脂联素在患有脓毒症的小鼠中减少。脂联素的定量逆转录聚合酶链反应显示出一种对模型和器官都具有特异性的反应模式。在脓毒症的挑战下，脂联素缺乏导致肺、肝和肾中内皮黏附和凝血分子的表达增加，通过逆转录聚合酶链反应定量，免疫组织化学显示巨噬细胞和中性粒细胞浸润增加，肝和肾中的血管渗漏增加。脂联素缺乏的小鼠在盲肠结扎和穿孔后存活率降低，血液中白细胞介素 6、可溶性血管内皮生长因子受体 1、可溶性内皮黏附分子 E-选择素和细胞间黏附分子 1 的水平升高。最后，ADPNKO 促进了肝脏和肾脏的终末器官损伤，而肺部未受影响。这些数据表明，脂联素在减少脓毒症期间微血管器官特异性内皮细胞激活方面具有保护作用。
