Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Obesity (Silver Spring). 2012 Mar;20(3):498-504. doi: 10.1038/oby.2011.316. Epub 2011 Oct 13.
Obesity increases circulating cell-endothelial cell interactions; an early marker of inflammation in laboratory model of sepsis, but little is known about the effect of different adipokines. Adiponectin is an anti-inflammatory adipokine secreted by adipocytes. Adiponectin deficiency is implicated in exaggerated proinflammatory phenotype in both obesity and sepsis via increased proinflammatory cytokine expression. However the effect of adiponectin deficiency on circulating cell-endothelial cell interactions in polymicrobial sepsis is unknown. Furthermore although brain dysfunction in septic patients is a known predictor of death, the pathophysiology involved is unknown. In the current study, we examined the effects of adiponectin deficiency on leukocyte (LA) and platelet adhesion (PA) in cerebral microcirculation of septic mice. Adiponectin deficient (Adipoq(-/-): Adko) and background strain C57Bl/6 (wild type (WT)) mice were used. Sepsis was induced using cecal ligation and puncture (CLP). We studied LA and PA in the cerebral microcirculation using intravital fluorescent video microscopy (IVM), blood brain barrier (BBB) dysfunction using Evans Blue (EB) leakage method and E-selectin expression using dual radiolabeling technique in different WT and Adko mice with CLP. Adiponectin deficiency significantly exaggerated LA (WT-CLP:201 ± 17; Adko-CLP: ± 53 cells/mm(2); P < 0.05) and PA (WT-CLP:125 ± 17; Adko-CLP:188 ± 20 cells/mm(2); P < 0.05) in cerebral microcirculation, EB leakage (WT-CLP:10 ± 3.7; Adko-CLP:24 ± 4.3 ng/g × µl plasma; P < 0.05) and E-selectin expression (WT-CLP:0.06 ± 0.11; Adko-CLP:0.44 ± 0.053 ng/g; P < 0.05) in the brain tissue of the mice with CLP. Furthermore, E-selectin monoclonal antibody (mAb) treatment attenuated cell adhesion and BBB dysfunction of Adko-CLP mice. Adiponectin deficiency is associated with exaggerated leukocyte and PA in cerebral microcirculation of mice with CLP via modulation of E-selectin expression.
肥胖会增加循环细胞与内皮细胞的相互作用；这是实验室脓毒症模型中炎症的早期标志物，但人们对不同脂肪因子的影响知之甚少。脂联素是一种由脂肪细胞分泌的抗炎脂肪因子。脂联素缺乏与肥胖和脓毒症中的促炎表型过度有关，这是通过增加促炎细胞因子的表达来实现的。然而，脂联素缺乏对多微生物脓毒症中循环细胞与内皮细胞相互作用的影响尚不清楚。此外，尽管脓毒症患者的脑功能障碍是死亡的已知预测因素，但涉及的病理生理学尚不清楚。在本研究中，我们研究了脂联素缺乏对脓毒症小鼠大脑微循环中白细胞（LA）和血小板黏附（PA）的影响。使用脂联素缺陷（Adipoq(-/-)：Adko）和背景品系 C57Bl/6（野生型（WT））小鼠。使用盲肠结扎和穿孔（CLP）诱导脓毒症。我们使用活体荧光视频显微镜（IVM）研究大脑微循环中的 LA 和 PA，使用 Evans Blue（EB）渗漏法研究血脑屏障（BBB）功能障碍，并使用双放射性标记技术研究不同 WT 和 Adko 小鼠的 E-选择素表达CLP。脂联素缺乏症显著加重了大脑微循环中的 LA（WT-CLP：201 ± 17；Adko-CLP：± 53 个细胞/mm(2)；P < 0.05）和 PA（WT-CLP：125 ± 17；Adko-CLP：188 ± 20 个细胞/mm(2)；P < 0.05）、大脑组织中的 EB 渗漏（WT-CLP：10 ± 3.7；Adko-CLP：24 ± 4.3 ng/g × µl 血浆；P < 0.05）和 E-选择素表达（WT-CLP：0.06 ± 0.11；Adko-CLP：0.44 ± 0.053 ng/g；P < 0.05）。此外，E-选择素单克隆抗体（mAb）治疗可减轻 Adko-CLP 小鼠的细胞黏附和 BBB 功能障碍。脂联素缺乏症通过调节 E-选择素表达与 CLP 小鼠大脑微循环中白细胞和 PA 的过度表达有关。
