The treatment with a ligand of Transcriptional Factor improves sepsis survival through anti-inflammatory effects

目的：感染性休克是重症监护病房仅次于心血管疾病的最常见死亡原因。不幸的是，目前还没有有效的治疗方法。据报道，过氧化物酶体增殖激活受体(PPAR)-配体可以减少炎症反应。为了评估PPAR-_Yligands改善脓毒性休克存活的假设，我们使用了一种脓毒症小鼠模型（载脂蛋白E （ApoE）敲除），并用PPAR-_Yligand吡格列酮治疗。由于缺乏内毒素清除，ApoE敲除小鼠在败血症中死亡率高。设计和设置；在大学实验室进行前瞻性实验室研究。实验对象：雄性ApoE敲除小鼠72只，野生型C57/B6小鼠60只，随机分为脓毒症、治疗前、治疗后三组。干预措施;脓毒症组和治疗组分别行盲肠结扎和穿刺。小鼠术前1天注射吡格列酮（5mg/kg/天）或术后6小时注射吡格列酮。测量结果和主要结果：术前和术后给予吡格列酮均能提高ApoE基因敲除和野生型小鼠的生存率。吡格列酮治疗组大鼠血清细胞因子、趋化因子水平及肺、肝髓过氧化物酶活性均受到抑制。吡格列酮还能抑制血流状态下单核细胞对血管内皮的粘附。结论：吡格列酮通过抑制炎症反应提高apoE基因敲除小鼠脓毒性休克后的存活率

Objective: Septic shock is the most common cause of death in intensive care unit next to cardiovascular diseases. Unfortunately, no effective treatment for this condition currently exists. Peroxisome proliferator-activated receptor (PPAR)-_Yligands are reported to reduce inflammatory responses. To evaluate the hypothesis that PPAR-_Yligands improve survival of septic shock, a mouse model of sepsis (apolipoprotein E (ApoE) knockout) was used and treated with pioglitazone, a PPAR-_Yligand. ApoE knockout mice have high mortality rate in sepsis due to lack of endotoxin clearance. Design and settings; Prospective laboratory study in a university laboratory. Subjects: Total 72 male ApoE knock out mice and 60 wild type C57/B6 mice randomized into three groups (sepsis, pre-treatment, post-treatment). Interventions; Cecal ligation and puncture were done in the sepsis and treatment groups. Mice injected with pioglitazone (5mg/kg/day) on the day before operation or mice injected with pioglitazone 6 hours after operation. Measurements and Main Results: Both pre- and post- operation treatment of pioglitazone improved survival of mortality in ApoE knock out and wild type mice. Serum levels of cytokines and chemokines, myeloperoxidase activity of lung and liver showed the same suppression in pioglitazone treatment group. Pioglitazone also suppressed monocytes adhesion to vascular endothelium under flow condition. Conclusions: Pioglitazone improved survival rate of apoE knockout mice after onset of septic shock through suppression of inflammatory respon