Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality
Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality
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DOI：
10.1016/j.surg.2009.01.010
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发表时间：
2009-05-01
期刊：
影响因子：
3.8
通讯作者：
Tani, Tohru
中科院分区：
文献类型：
--
作者：
Uji, Yoshitaka;Yamamoto, Hiroshi;Tani, Tohru
背景脂联素是代谢综合征的关键物质，具有抗炎作用。脂联素与体内脓毒症的关系尚不清楚。在这项研究中，脂联素可能参与多种微生物脓毒症进行了研究，使用脂联素敲除（APN-KO）小鼠进行盲肠结扎和穿刺（CLP），并接受过氧化物酶体增殖物激活受体γ（PPAR-gamma），增加血浆脂联素浓度。APN-KO和野生型（WT）小鼠经历CLP或假手术。分别于术前、术后2、4、6、8、12、16、24 h检测血浆脂联素、内毒素、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平，比较各组生存率。给小鼠注射罗格列酮（一种选择性PPAR-gamma激动剂），并比较CLP后与未注射罗格列酮的小鼠的存活率。CLP后，APN-KO小鼠的死亡率显著高于WT小鼠。CLP后24小时，APN-KO小鼠的血浆内毒素、TNF-α和IL-6水平显著高于WT小鼠。UP后4小时内，WT小鼠的血浆脂联素水平降至初始水平的一半。CLP前用PPAR-gamma治疗可增加血浆脂联素水平，并显著改善WT小鼠在脓毒症期间的死亡率; APN-KO小鼠的死亡率没有改善。这些结果提示脂联素缺乏可能导致多菌败血症小鼠的高死亡率和高炎症细胞因子水平。（Surgery 2009;145：550-7.）
Background. Adiponectin, a key substance in metabolic syndrome, is known to have anti-inflammatory properties. The relationship between adiponectin and sepsis in vivo is unclear. In this study, the possible involvement of adiponectin in polymicrobial sepsis was investigated using adiponectin-knockout (APN-KO) mice that underwent cecal ligation and puncture (CLP) and received the peroxisome proliferator-activated receptor gamma (PPAR-gamma) that increases the plasma adiponectin concentration.Methods. APN-KO and wild-type (WT) mice underwent either CLP or a sham operation. The plasma adiponectin, endotoxin, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were determined before and at 2, 4, 6, 8, 12, 16, and 24 hours after the procedures, and the survival rates were compared. Mice were injected with rosiglitazone, a selective PPAR-gamma agonist, and compared survival rates after CLP with those without rosiglitazone.Results. After CLP, APN-KO mice had a significantly higher mortality than WT mice. The plasma endotoxin, TNF-alpha, and IL-6 levels in APN-KO mice were significantly higher than those in WT mice 24 hours after CLP Within 4 hours after UP, the plasma adiponectin level in WT mice decreased to half of the initial levels. Pre-CLP treatment with PPAR-gamma was shown to increase the plasma adiponectin level and to improve significantly mortality of WT mice during sepsis; mortality among APN-KO mice did not improve.Conclusion. These results suggest that adiponectin deficiency may cause the high mortality and the high inflammatory cytokine levels in mice with polymicrobial sepsis. (Surgery 2009;145:550-7.)