Pioglitazone reduces inflammation through inhibition of NF-κB in polymicrobial sepsis.
Pioglitazone reduces inflammation through inhibition of NF-κB in polymicrobial sepsis.
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DOI：
10.1177/1753425913501565
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发表时间：
2014-07
期刊：
影响因子：
3.2
通讯作者：
Zingarelli B
中科院分区：
文献类型：
--
作者：
Kaplan J;Nowell M;Chima R;Zingarelli B
胰岛素增敏噻唑烷二酮类药物、罗格列酮和吡格列酮是特异性过氧化物酶体增殖物激活受体γ (PPARγ)激动剂，可降低2型糖尿病和冠状动脉疾病患者的促炎反应，可能对败血症有益。采用22g双穿刺技术，采用盲肠结扎穿刺法（CLP）诱导8-10周龄C57BL/6小鼠脓毒症。小鼠分别于CLP后1h和6h腹腔注射载药（DMSO:PBS）或吡格列酮（20mg/kg），并在不同时间点处死。在脓毒症中，给药小鼠出现低血糖，肺损伤加重，肺中性粒细胞浸润增加。脓毒症小鼠血浆促炎细胞因子升高，血浆脂肪因子脂联素降低。这与肺组织中抑制因子κB （IκBα）蛋白降解和NF-κB活性升高有关。吡格列酮治疗改善了血糖和脂联素水平，降低了促炎细胞因子。吡格列酮组小鼠肺IκBα蛋白表达升高，肺核因子κ b （NF-κB）活性降低。吡格列酮部分通过抑制NF-κB降低多微生物脓毒症的炎症反应，可能是一种新的脓毒症治疗方法。
The insulin sensitizing thiazolidinedione drugs, rosiglitazone and pioglitazone are specific peroxisome proliferator-activated receptor-gamma (PPARγ) agonists and reduce pro-inflammatory responses in patients with type 2 diabetes and coronary artery disease and may be beneficial in sepsis. Sepsis was induced in 8–10 wk old C57BL/6 mice by cecal ligation and puncture (CLP) with a 22g double puncture technique. Mice received intraperitoneal injection of vehicle (DMSO:PBS) or pioglitazone (20mg/kg) at 1h and 6h after CLP and were sacrificed at various timepoints. In sepsis, vehicle-treated mice had hypoglycemia, increased lung injury and increased lung neutrophil infiltration. Pro-inflammatory plasma cytokines were increased but the plasma adipokine, adiponectin, was decreased in vehicle-treated septic mice. This corresponded with inhibitor κB (IκBα) protein degradation and an increase in NF-κB activity in lung. Pioglitazone treatment improved plasma glucose and adiponectin levels and decreased pro-inflammatory cytokines. Lung IκBα protein expression increased and corresponded with a decrease in nuclear factor kappa-B (NF-κB) activity in the lung from pioglitazone treated mice. Pioglitazone reduces the inflammatory response in polymicrobial sepsis in part through inhibition of NF-κB and may be a novel therapy in sepsis.
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