Pioglitazone reduces systematic inflammation and improves mortality in apolipoprotein E knockout mice with sepsis
Pioglitazone reduces systematic inflammation and improves mortality in apolipoprotein E knockout mice with sepsis
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DOI：
10.1007/s00134-008-1024-9
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发表时间：
2008-07-01
影响因子：
38.9
通讯作者：
Isobe, Mitsuaki
中科院分区：
文献类型：
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作者：
Haraguchi, Go;Kosuge, Hisanori;Isobe, Mitsuaki
目的：为了确定过氧化物酶体增殖物激活受体（PPAR）γ配体是否能改善脓毒性休克患者的生存率，我们用吡格列酮（一种PPAR-γ配体）治疗了脓毒症小鼠模型[载脂蛋白（Apo）E）敲除小鼠]。ApoE敲除小鼠由于败血症具有高死亡率，因为内毒素未被清除。设计和设置：在大学实验室的前瞻性研究。研究对象：我们将87只雄性ApoE基因敲除小鼠和60只野生型C57/B6小鼠随机分为三组（脓毒症组、治疗前组和治疗后组）。干预措施：脓毒症组和治疗组进行盲肠结扎和穿刺（CLP）。在CLP前一天或手术后6 h给小鼠注射吡格列酮（5 mg/kg/天）。测量和结果：CLP治疗前后吡格列酮均改善了ApoE基因敲除小鼠和野生型小鼠的存活率。吡格列酮治疗组的血清细胞因子和趋化因子水平以及肺和肝中的髓过氧化物酶活性受到抑制。吡格列酮也抑制单核细胞粘附到血管内皮细胞在流动条件下。结论：吡格列酮通过抑制炎症反应改善感染性休克后ApoE基因敲除小鼠的存活率。
Objective: To determine whether peroxisome proliferator-activated receptor (PPAR) gamma ligands improve survival of patients with septic shock we treated a mouse model of sepsis [apolipoprotein (Apo) E) knockout mice] with pioglitazone, a PPAR-gamma ligand. ApoE knockout mice have a high mortality rate due to sepsis because the endotoxin is not cleared. Design and setting: Prospective study in a university laboratory. Subjects: We assorted 87 male ApoE knockout mice and 60 wild-type C57/B6 mice randomly into three groups (sepsis, pretreatment, posttreatment). Interventions: Cecal ligation and puncture (CLP) was carried out in the sepsis and treatment groups. Mice were injected with pioglitazone (5 mg/kg per day) on the day before CLP or 6 h after surgery. Measurements and results: Both pre-and post-CLP treatment with pioglitazone improved survival of ApoE knockout and wild-type mice. Serum levels of cytokines and chemokines and myeloperoxidase activity in lung and liver were suppressed in the pioglitazone-treated group. Pioglitazone also suppressed monocyte adhesion to vascular endothelium under flow conditions. Conclusions: Pioglitazone improved survival of ApoE knockout mice after onset of septic shock through suppression of inflammatory responses.