ADIPONECTIN DIMINISHES ORGAN-SPECIFIC MICROVASCULAR ENDOTHELIAL CELL ACTIVATION ASSOCIATED WITH SEPSIS

作者：van Meurs Matijs^*; Castro Pedro; Shapiro Nathan I; Lu Shulin; Yano Midori; Maeda Norikazu; Funahashi Tohru; Shimomura Ichiro; Zijlstra Jan G; Molema Grietje; Parikh Samir M; Aird William C; Yano Kiichiro

来源：Shock, 2012, 37(4): 392-398.

DOI：10.1097/SHK.0b013e318248225e

• Adiponectin
• sepsis
• endothelium
• multiple organ dysfunction
• adhesion molecules

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.

• 出版日期2012-4